Method for evaluating drug sensitivity and disease vulnerability by analyzing cyclic amp responsive element binding protein gene

Abstract

The present invention provides a method for evaluating (predicting, etc.) an individual difference (the tendency of every individual) in terms of drug sensitivity and disease vulnerability, comprising using a gene polymorphism of a cyclic AMP responsive element binding protein gene or the like. The method for evaluating drug sensitivity and the method for evaluating disease vulnerability according to the present invention comprise associating a gene polymorphism of a cyclic AMP responsive element binding protein gene or a haplotype constituted by the gene polymorphism with the drug sensitivity and disease vulnerability of an individual.

1 . A method for evaluating drug sensitivity, comprising associating a gene polymorphism of a cyclic AMP responsive element binding protein gene or a haplotype constituted by the gene polymorphism with an individual drug sensitivity. 
     
     
         2 . The method according to  claim 1 , wherein a tendency in the presence or absence of an individual drug sensitivity is evaluated based on the results from the analysis of the gene polymorphism or the haplotype. 
     
     
         3 . The method according to  claim 1 , comprising the following steps:
 (1) a step of performing linkage disequilibrium analysis and haplotype analysis on a healthy subject and selecting gene polymorphisms in a linkage disequilibrium block;   (2) a step of analyzing the association between the genotypes of the gene polymorphisms and drug sensitivity in a test subject; and   (3) a step of using the gene polymorphism that has been significantly associated with drug sensitivity in the test subject for evaluation of the drug sensitivity.   
     
     
         4 . A method for evaluating disease vulnerability, comprising associating a gene polymorphism of a cyclic AMP responsive element binding protein gene or a haplotype constituted by the gene polymorphism with an individual disease vulnerability. 
     
     
         5 . The method according to  claim 4 , wherein a tendency in the presence or absence of an individual disease vulnerability is evaluated based on the results from the analysis of the gene polymorphism or the haplotype. 
     
     
         6 . The method according to  claim 4 , comprising the following steps:
 (1) a step of performing linkage disequilibrium analysis and haplotype analysis on a healthy subject and selecting gene polymorphisms in a linkage disequilibrium block;   (2) a step of comparing the frequency of gene polymorphisms in a test subject with the frequency of gene polymorphisms in the healthy subject; and   (3) a step of using the gene polymorphism that has a significant difference in the gene polymorphism frequency between the test subject and the healthy subject for evaluation of the disease vulnerability.   
     
     
         7 . The method according to  claim 4 , wherein the disease vulnerability is pain sensitivity or vulnerability to substance dependence. 
     
     
         8 . The method according to  claim 1  or  4 , wherein the gene polymorphism is at least one selected from the group consisting of a single nucleotide polymorphism, an insertion polymorphism, a deletion polymorphism, and a nucleotide repeat polymorphism. 
     
     
         9 . The method according to  claim 1  or  4 , wherein the gene polymorphism is at least one selected from among: rs16839837, rs2360969, rs10932200, rs2253206, rs2551640, rs11904814, rs16839883, rs6740584, rs3770704, rs2254137, rs2551645, rs2551946, rs4234080, rs2952768, rs2709386, rs7591784, and rs7594560 of a CREB1 subtype gene; rs1243872, rs2145925, rs2025126, rs1885373, rs1885374, GA007473, rs2295794, rs4879926, GA007477, rs867194, rs11541908, rs741917, rs7862485, rs2756894, rs2249250, rs2295795, rs877365, rs2737273, rs2295797, rs2295798, rs1534847, rs7873822, rs2737274, rs10972567, rs3763630, rs10814274, rs3750434, rs1570246, GA025684, rs1570248, rs1570249, rs34478611, rs1322045, rs1951432, GA025687, rs10814275, rs10758320, rs4878628, rs10758321, and rs10758322 of a CREB3 subtype gene; rs4722778, rs177479, rs177480, rs11981754, rs177486, rs177498, rs2175738, rs17156579, rs17156603, rs17642145, rs10229500, rs10243659, rs4722785, rs16874503, rs11772815, rs6958133, rs16874525, rs17715174, rs6953524, rs10239810, rs17156649, rs1811248, rs887623, rs740988, rs7794304, rs6952227, rs42695, rs1029897, rs4722793, rs10233653, rs6955105, rs17156685, rs17156694, rs17156699, rs177572, rs177573, rs177574, rs177576, rs13437706, rs177580, rs177581, rs12666636, rs177584, rs177585, rs216715, rs10951197, rs160335, rs1008262, rs310353, rs310359, rs41273, rs1637457, rs17156919, rs41276, rs160375, rs917275, rs41348, rs886816, rs17157048, rs6462098, rs10951201, rs13311248, rs12540480, rs10265166, rs7798774, rs7799246, rs6972081, rs12533079, rs7806547, rs6462100, rs6979352, rs6950574, rs4722835, rs2066979, rs10486591, rs721993, rs2237351, rs3735566, rs11975539, rs6462107, rs2190306, rs4719955, and rs10228137 of a CREB5 subtype gene; and rs1153711, rs1153702, rs7583431, rs1153699, rs2302663, rs3845744, rs212349, rs212347, rs12693057, rs1153685, rs212360, rs212361, rs2072538, rs1205399, rs1153676, rs7566401, rs7578569, rs3755490, rs13388308, rs11888507, rs10497434, rs268214, rs166531, rs268228, rs268229, rs268230, rs268231, rs10497435, rs1982235, rs268237, rs13030474, and rs268174 of an ATF2 subtype gene. 
     
     
         10 . The method according to  claim 1  or  4 , wherein the haplotype is at least one selected from the following table. 
       
         
           
                 
               
                   TABLE 1  
                 
                     
                 
                   Gene name CREB1 
                 
                 
                 
               
                     
                   Linkage disequilibrium block No. 
                 
                     
                   1 
                 
                     
                   Gene polymorphism name () 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
               
                     
                   1 
                   2 
                   3 
                     
                     
                     
                     
                     
                     
                     
                     
                   12 
                   13 
                     
                     
                     
                   17 
                 
                   Haplotype No. 
                   Tag 
                   Tag 
                   Tag 
                   4 
                   5 
                   6 
                   7 
                   8 
                   9 
                   10 
                   11 
                   Tag 
                   Tag 
                   14 
                   15 
                   16 
                   Tag 
                 
                     
                 
                   H1 
                   C 
                   C 
                   C 
                   A 
                   G 
                   G 
                   G 
                   T 
                   C 
                   C 
                   C 
                   C 
                   C 
                   C 
                   A 
                   A 
                   T 
                 
                   H2 
                   C 
                   C 
                   A 
                   G 
                   A 
                   T 
                   A 
                   C 
                   T 
                   A 
                   T 
                   C 
                   C 
                   T 
                   G 
                   G 
                   T 
                 
                   H3 
                   C 
                   T 
                   C 
                   A 
                   G 
                   G 
                   A 
                   T 
                   T 
                   C 
                   C 
                   C 
                   C 
                   C 
                   A 
                   A 
                   T 
                 
                   H4 
                   T 
                   C 
                   A 
                   G 
                   A 
                   T 
                   A 
                   C 
                   T 
                   A 
                   T 
                   C 
                   A 
                   T 
                   G 
                   G 
                   C 
                 
                   H5 
                   C 
                   C 
                   A 
                   G 
                   A 
                   T 
                   A 
                   C 
                   T 
                   A 
                   T 
                   A 
                   C 
                   C 
                   A 
                   A 
                   T 
                 
                   H6 
                   T 
                   C 
                   A 
                   G 
                   A 
                   T 
                   A 
                   C 
                   T 
                   A 
                   T 
                   C 
                   C 
                   T 
                   G 
                   G 
                   T 
                 
                   H7 
                   T 
                   C 
                   A 
                   G 
                   A 
                   T 
                   A 
                   C 
                   T 
                   A 
                   T 
                   C 
                   A 
                   T 
                   G 
                   G 
                   T 
                 
                 
                 
               
                   . . . 
                   Haplotypes which are estimated to occur at a frequency of less than 1% 
                 
                     
                 
                   () 1~17: (in this order)rs16839837, rs2360969, rs10932200, rs2253206, rs2551640, rs11904814, rs16839883, rs6740584, rs3770704, rs2254137, rs2551645, rs2551946, rs4234080, rs2952768, rs2709386, rs7591784 and rs7594560 
                 
             
                
               
               
                
                
               
            
             
                
                
                
               
            
             
                
                
                
                
                
                
                
                
                
                
               
            
             
                
                
                
               
            
           
         
       
       
         
           
                 
               
                   TABLE 2  
                 
                     
                 
                   Gene name CREB3 
                 
                     
                 
                     
                 
                 
                 
               
                     
                   Linkage disequilibrium block No. 
                 
                     
                   1 
                 
                     
                   Gene polymorphism name () 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
               
                     
                   1 
                   2 
                   3 
                     
                     
                     
                     
                     
                   9 
                     
                   11 
                     
                     
                     
                     
                     
                     
                     
                     
                     
                     
                     
                     
                     
                 
                   Haplotype No. 
                   Tag 
                   Tag 
                   Tag 
                   4 
                   5 
                   6 
                   7 
                   8 
                   Tag 
                   10 
                   Tag 
                   12 
                   13 
                   14 
                   15 
                   16 
                   17 
                   18 
                   19 
                   20 
                   21 
                   22 
                   23 
                   24 
                 
                     
                 
                   H1 
                   G 
                   C 
                   G 
                   T 
                   A 
                   T 
                   T 
                   T 
                   C 
                   T 
                   C 
                   C 
                   G 
                   C 
                   T 
                   G 
                   T 
                   G 
                   T 
                   C 
                   A 
                   G 
                   G 
                   A 
                 
                   H2 
                   G 
                   C 
                   G 
                   T 
                   A 
                   T 
                   T 
                   T 
                   T 
                   T 
                   C 
                   C 
                   G 
                   C 
                   T 
                   G 
                   T 
                   G 
                   T 
                   C 
                   A 
                   G 
                   G 
                   A 
                 
                   H3 
                   T 
                   T 
                   A 
                   T 
                   A 
                   T 
                   C 
                   T 
                   C 
                   T 
                   T 
                   C 
                   G 
                   A 
                   G 
                   A 
                   C 
                   A 
                   C 
                   C 
                   G 
                   T 
                   G 
                   C 
                 
                   H4 
                   T 
                   T 
                   A 
                   T 
                   A 
                   T 
                   C 
                   T 
                   C 
                   T 
                   C 
                   C 
                   G 
                   A 
                   G 
                   A 
                   C 
                   A 
                   C 
                   C 
                   G 
                   T 
                   G 
                   C 
                 
                   H5 
                   T 
                   C 
                   G 
                   C 
                   C 
                   C 
                   C 
                   C 
                   C 
                   T 
                   C 
                   C 
                   A 
                   A 
                   G 
                   G 
                   C 
                   A 
                   T 
                   C 
                   A 
                   T 
                   A 
                   C 
                 
                   H6 
                   T 
                   T 
                   G 
                   T 
                   A 
                   T 
                   C 
                   T 
                   C 
                   C 
                   C 
                   T 
                   G 
                   A 
                   T 
                   G 
                   C 
                   G 
                   T 
                   C 
                   A 
                   G 
                   G 
                   C 
                 
                   H7 
                   T 
                   C 
                   A 
                   T 
                   A 
                   T 
                   C 
                   T 
                   C 
                   T 
                   T 
                   C 
                   G 
                   A 
                   G 
                   A 
                   C 
                   A 
                   G 
                   C 
                   G 
                   T 
                   G 
                   C 
                 
                 
                 
               
                   . . . 
                   Haplotypes which are estimated to occur at a frequency of less than 1% 
                 
                     
                 
                 
                 
               
                     
                   Linkage disequilibrium block No. 
                 
                     
                   2 
                 
                     
                   Gene polymorphism name () 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
               
                     
                   25 
                   26 
                     
                     
                   29 
                     
                     
                     
                     
                     
                     
                   36 
                     
                   38 
                   39 
                     
                 
                   Haplotype No. 
                   Tag 
                   Tag 
                   27 
                   28 
                   Tag 
                   30 
                   31 
                   32 
                   33 
                   34 
                   35 
                   Tag 
                   37 
                   Tag 
                   Tag 
                   40 
                 
                     
                 
                   H8 
                   C 
                   C 
                   G 
                   G 
                   G 
                   C 
                   G 
                   G 
                   G 
                   A 
                   T 
                   A 
                   C 
                   C 
                   G 
                   C 
                 
                   H9 
                   C 
                   T 
                   A 
                   T 
                   G 
                   T 
                   A 
                   G 
                   A 
                   G 
                   A 
                   A 
                   T 
                   C 
                   A 
                   T 
                 
                   H10 
                   T 
                   C 
                   G 
                   G 
                   C 
                   T 
                   G 
                   A 
                   A 
                   G 
                   A 
                   A 
                   T 
                   C 
                   G 
                   C 
                 
                   H11 
                   C 
                   T 
                   A 
                   G 
                   G 
                   T 
                   A 
                   G 
                   A 
                   G 
                   A 
                   A 
                   T 
                   C 
                   G 
                   T 
                 
                   H12 
                   C 
                   C 
                   G 
                   G 
                   C 
                   T 
                   G 
                   A 
                   A 
                   G 
                   A 
                   A 
                   T 
                   C 
                   G 
                   C 
                 
                   H13 
                   C 
                   T 
                   A 
                   T 
                   G 
                   T 
                   A 
                   G 
                   A 
                   G 
                   A 
                   G 
                   T 
                   C 
                   A 
                   T 
                 
                   H14 
                   C 
                   C 
                   G 
                   G 
                   G 
                   C 
                   G 
                   G 
                   G 
                   A 
                   T 
                   A 
                   C 
                   T 
                   G 
                   C 
                 
                 
                 
               
                   . . . 
                   Haplotypes which are estimated to occur at a frequency of less than 1% 
                 
                     
                 
                   () 1~40: (in this order)rs1243872, rs2145925, rs2025126, rs1885373, rs1885374, GA007473, rs2295794, rs4879926, GA007477, rs867194, rs11541908, rs741917, rs7862485, rs2756894, rs2249250, rs2295795, rs877365, rs2737273, rs2295797, rs2295798, rs1534847, rs7873822, rs2737274, rs10972567, rs3763630, rs10814274, rs3750434, rs1570246, GA025684, rs1570248, rs1570249, rs34478611, rs1322045, rs1951432, GA025687, rs10814275, rs10758320, rs4878628, rs10758321 and rs10758322 
                 
             
                
                
                
                
               
               
                
               
            
             
                
                
                
               
            
             
                
                
                
                
                
                
                
                
                
                
               
            
             
                
                
               
            
             
                
                
                
               
            
             
                
                
                
                
                
                
                
                
                
                
               
            
             
                
                
                
               
            
           
         
       
       
         
           
                 
               
                   TABLE 3  
                 
                     
                 
                   Gene name crEB5 
                 
                     
                 
                     
                 
                 
                 
               
                     
                   Linkage disequilibrium block No. 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
               
                     
                   1 
                     
                   5 
                     
                   6 
                     
                   9 
                     
                   10 
                 
                 
                 
               
                     
                   Gene polymorphism name () 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
               
                     
                   1 
                   2 
                     
                     
                   5 
                   6 
                     
                   7 
                   8 
                   9 
                     
                   11 
                     
                     
                   13 
                   14 
                     
                   15 
                   16 
                     
                   17 
                   18 
                 
                   Haplotype (H) No. 
                   Tag 
                   Tag 
                   3 
                   4 
                   Tag 
                   Tag 
                   H No. 
                   Tag 
                   Tag 
                   Tag 
                   10 
                   Tag 
                   12 
                   H No. 
                   Tag 
                   Tag 
                   H No. 
                   Tag 
                   Tag 
                   H No. 
                   Tag 
                   Tag 
                 
                     
                 
                   H1 
                   C 
                   T 
                   A 
                   A 
                   G 
                   C 
                   H6 
                   C 
                   C 
                   G 
                   C 
                   A 
                   G 
                   H11 
                   T 
                   G 
                   H14 
                   T 
                   A 
                   H17 
                   G 
                   T 
                 
                   H2 
                   G 
                   C 
                   G 
                   A 
                   G 
                   T 
                   H7 
                   C 
                   A 
                   A 
                   C 
                   G 
                   G 
                   H12 
                   C 
                   C 
                   H15 
                   C 
                   A 
                   H18 
                   G 
                   G 
                 
                   H3 
                   G 
                   C 
                   G 
                   A 
                   A 
                   T 
                   H8 
                   C 
                   C 
                   G 
                   C 
                   G 
                   G 
                   H13 
                   C 
                   G 
                   H16 
                   C 
                   G 
                   H19 
                   A 
                   G 
                 
                   H4 
                   C 
                   C 
                   G 
                   A 
                   G 
                   T 
                   H9 
                   T 
                   A 
                   A 
                   C 
                   G 
                   A 
                   . . . 
                     
                     
                   . . . 
                     
                     
                   . . . 
                 
                   H5 
                   G 
                   C 
                   G 
                   A 
                   G 
                   C 
                   H10 
                   C 
                   C 
                   A 
                   C 
                   G 
                   G 
                 
                 
                 
               
                   . . . 
                   Haplotypes which are estimated to occur at a frequency of less than 1% 
                 
                     
                 
                 
                 
               
                     
                   Linkage disequilibrium block No. 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
               
                     
                   11 
                     
                   12 
                     
                   13 
                     
                   15 
                     
                   16 
                 
                 
                 
               
                     
                   Gene polymorphism name () 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
               
                     
                   19 
                   20 
                     
                   21 
                   22 
                   23 
                     
                   24 
                   25 
                     
                   26 
                   27 
                   28 
                     
                   29 
                   30 
                   31 
                     
                     
                 
                   Haplotype (H) No. 
                   Tag 
                   Tag 
                   H No. 
                   Tag 
                   Tag 
                   Tag 
                   H No. 
                   Tag 
                   Tag 
                   H No. 
                   Tag 
                   Tag 
                   Tag 
                   H No. 
                   Tag 
                   Tag 
                   Tag 
                   32 
                   33 
                 
                     
                 
                   H20 
                   T 
                   A 
                   H24 
                   G 
                   C 
                   C 
                   H28 
                   A 
                   A 
                   H31 
                   G 
                   T 
                   C 
                   H35 
                   C 
                   C 
                   C 
                   G 
                   C 
                 
                   H21 
                   T 
                   G 
                   H25 
                   G 
                   C 
                   T 
                   H29 
                   G 
                   A 
                   H32 
                   A 
                   C 
                   T 
                   H36 
                   T 
                   C 
                   A 
                   G 
                   C 
                 
                   H22 
                   C 
                   G 
                   H26 
                   A 
                   C 
                   T 
                   H30 
                   G 
                   G 
                   H33 
                   A 
                   T 
                   T 
                   H37 
                   C 
                   C 
                   A 
                   G 
                   C 
                 
                   H23 
                   C 
                   A 
                   H27 
                   G 
                   T 
                   T 
                   . . . 
                     
                     
                   H34 
                   A 
                   T 
                   C 
                   H38 
                   T 
                   T 
                   C 
                   A 
                   T 
                 
                 
                 
               
                   . . . 
                   Haplotypes which are estimated to occur at a frequency of less than 1% 
                 
                     
                 
                 
                 
               
                     
                   Linkage disequilibrium block No. 
                 
                 
                 
                 
                 
                 
                 
                 
                 
               
                     
                   25 
                     
                   26 
                     
                   27 
                     
                   32 
                 
                 
                 
               
                     
                   Gene polymorphism name () 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
               
                     
                   34 
                   35 
                     
                   36 
                   37 
                   38 
                   39 
                     
                   40 
                     
                     
                   42 
                   43 
                   44 
                   45 
                     
                   47 
                     
                     
                   50 
                 
                   Haplotype (H) No. 
                   Tag 
                   Tag 
                   H No. 
                   Tag 
                   Tag 
                   Tag 
                   Tag 
                   H No. 
                   Tag 
                   41 
                   H No. 
                   Tag 
                   Tag 
                   Tag 
                   Tag 
                   46 
                   Tag 
                   48 
                   49 
                   Tag 
                 
                     
                 
                   H39 
                   T 
                   A 
                   H42 
                   G 
                   A 
                   G 
                   G 
                   H47 
                   A 
                   A 
                   H49 
                   A 
                   T 
                   C 
                   G 
                   T 
                   G 
                   T 
                   T 
                   T 
                 
                   H40 
                   C 
                   G 
                   H43 
                   G 
                   A 
                   A 
                   A 
                   H48 
                   G 
                   G 
                   H50 
                   A 
                   T 
                   C 
                   G 
                   T 
                   G 
                   T 
                   T 
                   C 
                 
                   H41 
                   T 
                   G 
                   H44 
                   A 
                   G 
                   G 
                   A 
                   . . . 
                     
                     
                   H51 
                   A 
                   T 
                   A 
                   C 
                   C 
                   G 
                   T 
                   C 
                   C 
                 
                   . . . 
                     
                     
                   H45 
                   G 
                   A 
                   G 
                   A 
                     
                     
                     
                   H52 
                   C 
                   T 
                   A 
                   C 
                   T 
                   T 
                   C 
                   T 
                   C 
                 
                     
                     
                     
                   H46 
                   G 
                   G 
                   G 
                   A 
                     
                     
                     
                   H53 
                   C 
                   T 
                   A 
                   C 
                   T 
                   G 
                   C 
                   T 
                   C 
                 
                     
                     
                     
                   . . . 
                     
                     
                     
                     
                     
                     
                     
                   H54 
                   A 
                   C 
                   C 
                   G 
                   T 
                   G 
                   T 
                   T 
                   T 
                 
                     
                     
                     
                     
                     
                     
                     
                     
                     
                     
                     
                   H55 
                   A 
                   T 
                   A 
                   G 
                   T 
                   G 
                   T 
                   T 
                   C 
                 
                 
                 
               
                     
                   Haplotypes which are estimated to occur at a frequency of less than 1% 
                 
                     
                     
                 
                 
                 
               
                     
                   Linkage disequilibrium block No. 
                 
                 
                 
                 
                 
                 
                 
               
                     
                   33 
                     
                   35 
                     
                   40 
                 
                 
                 
               
                     
                   Gene polymorphism name () 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
               
                     
                   51 
                   52 
                   53 
                   54 
                     
                     
                     
                   57 
                   58 
                     
                   59 
                     
                     
                     
                     
                     
                 
                   Haplotype (H) No. 
                   Tag 
                   Tag 
                   Tag 
                   Tag 
                   55 
                   56 
                   H No. 
                   Tag 
                   Tag 
                   H No. 
                   Tag 
                   60 
                   61 
                   62 
                   63 
                   64 
                 
                     
                 
                   H56 
                   T 
                   G 
                   G 
                   C 
                   A 
                   A 
                   H61 
                   C 
                   T 
                   H64 
                   G 
                   G 
                   C 
                   T 
                   T 
                   C 
                 
                   H57 
                   T 
                   A 
                   A 
                   T 
                   G 
                   C 
                   H62 
                   T 
                   C 
                   H65 
                   A 
                   A 
                   T 
                   C 
                   C 
                   A 
                 
                   H58 
                   G 
                   A 
                   A 
                   C 
                   G 
                   C 
                   H63 
                   T 
                   T 
                   . . . 
                 
                   H59 
                   T 
                   A 
                   G 
                   C 
                   A 
                   A 
                   . . . 
                 
                   H60 
                   T 
                   A 
                   A 
                   C 
                   G 
                   C 
                 
                 
                 
               
                   . . . 
                   Haplotypes which are estimated to occur at a frequency of less than 1% 
                 
                     
                 
                   () 1~64: (in this order)rs4722778, rs177479, rs177480, rs11981754, rs177486, rs177498, rs10229500, rs10243659, rs4722785, rs16874503, rs11772815, rs6958133, rs16874525, rs17715174, rs6953524, rs10239810, rs17156649, rs1811248, rs887623, rs740988, rs6952227, rs42695, rs1029897, rs10233653, rs6955105, rs17156699, rs177572, rs177573, rs177580, rs177581, rs12666636, rs177584, rs177585, rs1008262, rs310353, rs41273, rs1637457, rs17156919, rs41276, rs160375, rs917275, rs17157048, rs6462098, rs10951201, rs13311248, rs12540480, rs10265166, rs7798774, rs7799246, rs6972081, rs12533079, rs7806547, rs6462100, rs6979352, rs6950574, rs4722835, rs721993, rs2237351, rs3735566, rs11975539, rs6462107, rs2190306, rs4719955 and rs10228137 
                 
             
                
                
                
                
               
               
                
               
            
             
                
               
            
             
                
               
            
             
                
               
            
             
                
                
                
                
                
                
                
                
               
            
             
                
                
               
            
             
                
               
            
             
                
               
            
             
                
               
            
             
                
                
                
                
                
                
                
               
            
             
                
                
               
            
             
                
               
            
             
                
               
            
             
                
               
            
             
                
                
                
                
                
                
                
                
                
                
               
            
             
                
                
               
            
             
                
               
            
             
                
               
            
             
                
               
            
             
                
                
                
                
                
                
                
                
               
            
             
                
                
                
               
            
           
         
       
       
         
           
                 
               
                   TABLE 4  
                 
                     
                 
                   Gene name ATF2 
                 
                     
                 
                     
                 
                 
                 
               
                     
                   Linkage disequilibrium block No. 
                 
                 
                 
                 
               
                     
                   1 
                   2 
                 
                 
                 
               
                     
                   Gene polymorphism name () 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
               
                     
                   1 
                   2 
                   3 
                   4 
                   5 
                     
                     
                     
                     
                     
                     
                     
                     
                     
                     
                     
                 
                   Haplotype No. 
                   Tag 
                   Tag 
                   Tag 
                   Tag 
                   Tag 
                   6 
                   7 
                   8 
                   9 
                   10 
                   11 
                   12 
                   13 
                   14 
                   15 
                   16 
                 
                     
                 
                   H1 
                   T 
                   C 
                   A 
                   A 
                   G 
                   C 
                   C 
                   A 
                   G 
                   C 
                   G 
                   T 
                   C 
                   A 
                   A 
                   A 
                 
                   H2 
                   G 
                   C 
                   A 
                   G 
                   G 
                   T 
                   T 
                   G 
                   A 
                   T 
                   A 
                   C 
                   A 
                   C 
                   C 
                   G 
                 
                   H3 
                   T 
                   T 
                   C 
                   G 
                   A 
                   T 
                   T 
                   G 
                   A 
                   T 
                   A 
                   C 
                   A 
                   C 
                   C 
                   G 
                 
                   H4 
                   T 
                   T 
                   A 
                   G 
                   A 
                   T 
                   T 
                   G 
                   A 
                   T 
                   A 
                   C 
                   A 
                   C 
                   C 
                   G 
                 
                     
                     
                     
                     
                   G 
                   G 
                   T 
                   T 
                   G 
                   A 
                   T 
                   A 
                   C 
                   A 
                   C 
                   C 
                   G 
                 
                 
                 
               
                   . . . 
                   Haplotypes which are estimated to occur at a frequency of less than 1% 
                 
                     
                 
                     
                   Linkage disequilibrium block No. 
                 
                     
                   2 
                 
                     
                   Gene polymorphism name () 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
               
                     
                     
                     
                     
                     
                   21 
                     
                     
                     
                     
                     
                     
                   28 
                     
                     
                     
                 
                   Haplotype No. 
                   17 
                   18 
                   19 
                   20 
                   Tag 
                   22 
                   23 
                   24 
                   25 
                   26 
                   27 
                   Tag 
                   29 
                   30 
                   31 
                 
                     
                 
                   H5 
                   C 
                   T 
                   T 
                   C 
                   C 
                   C 
                   G 
                   A 
                   C 
                   A 
                   C 
                   T 
                   T 
                   G 
                   T 
                 
                   H6 
                   T 
                   C 
                   C 
                   T 
                   T 
                   T 
                   A 
                   G 
                   A 
                   C 
                   T 
                   G 
                   C 
                   G 
                   C 
                 
                   H7 
                   T 
                   C 
                   C 
                   T 
                   T 
                   T 
                   A 
                   G 
                   A 
                   C 
                   T 
                   T 
                   C 
                   G 
                   C 
                 
                   H8 
                   T 
                   C 
                   C 
                   T 
                   T 
                   T 
                   A 
                   G 
                   A 
                   C 
                   T 
                   G 
                   C 
                   G 
                   C 
                 
                   H9 
                   T 
                   C 
                   C 
                   T 
                   C 
                   C 
                   G 
                   A 
                   C 
                   A 
                   C 
                   T 
                   T 
                   G 
                   T 
                 
                 
                 
               
                   . . . 
                   Haplotypes which are estimated to occur at a frequency of less than 1% 
                 
                     
                 
                   () 1~31: (in this order)rs1153711, rs1153702, rs7583431, rs2302663, rs3845744, s212349, rs212347, rs12693057, rs1153685, rs212360, rs212361, rs2072538, rs1205399, rs1153676, rs7566401, rs7578569, rs3755490, rs13388308, rs11888507, rs10497434, rs268214, rs166531, rs268228, rs268229, rs268230, rs268231, rs10497435, rs1982235, rs268237, rs13030474 and rs268174 
                 
             
                
                
                
                
               
               
                
               
            
             
                
               
            
             
                
               
            
             
                
               
            
             
                
                
                
                
                
                
                
                
               
            
             
                
                
                
                
                
               
            
             
                
                
                
                
                
                
                
                
               
            
             
                
                
                
               
            
           
         
       
     
     
         11 . A method for determining the type, amount, and/or frequency of administration of a drug to be administered to an individual, comprising using the result from the evaluation by the method according to  claim 1  or  4  as an index. 
     
     
         12 . A method for predicting a side effect of a drug to be administered to an individual, comprising using the result from the evaluation by the method according to  claim 1  or  4  as an index. 
     
     
         13 . The method according to  claim 1  or  7 , wherein the drug is an opioid receptor function modulator and/or a cyclic AMP responsive element binding protein function modulator. 
     
     
         14 . The method according to  claim 13 , wherein the opioid receptor function modulator is at least one selected from the group consisting of methamphetamine, methylenedioxymethamphetamine, amphetamine, dextroamphetamine, dopamine, morphine, DAMGO, codeine, methadone, carfentanil, fentanyl, heroin, cocaine, naloxone, naltrexone, nalorphine, levallorphan, pentazocine, pethidine, buprenorphine, oxycodone, hydrocodone, levorphanol, etorphine, dihydroetorphine, hydromorphone, oxymorphone, tramadol, diclofenac, indomethacin, flurbiprofen axetil, marcaine, ethanol, methanol, diethyl ether, propanol, butanol, flupirtine, laughing gas, F3 (1-chloro-1,2,2-trifluorocyclobutane), halothane, estradiol, dithiothreitol, thioridazine, pimozide, fluoxetine, paroxetine, desipramine, imipramine, clomipramine, tetramide, isoflurane, ginsenoside, ifenprodil, bupivacaine, tertiapin, clozapine, haloperidol, SCH23390, and cocaine; and the cyclic AMP responsive element binding protein function modulator is at least one selected from the group consisting of phosphodiesterase 4 (PDE4), calcineurin, protein kinase A, protein kinase C, p90 ribosome S6 kinase 1 (RSK1), calmodulin kinase, glycogen synthase kinase 3β, and CREB-regulated transcription coactivator 1 (CRTC1). 
     
     
         15 . The method according to  claim 1  or  4 , comprising using an oligonucleotide consisting of a nucleotide sequence of at least 10 nucleotides comprising the 51 st  nucleotide of the nucleotide sequence represented by any one of SEQ ID NOS: 1 to 172, or a complementary nucleotide sequence thereto, which can specifically hybridize to a DNA fragment comprising a gene polymorphism of a cyclic AMP responsive element binding protein gene. 
     
     
         16 . The method according to  claim 15 , wherein the oligonucleotide spans a length of 10 to 150 nucleotides. 
     
     
         17 . The method according to  claim 15 , wherein the oligonucleotide is selected from the group consisting of the nucleotide sequence represented by any one of SEQ ID NOS: 1 to 172 and a complementary nucleotide sequence thereto. 
     
     
         18 . A gene polymorphism marker for evaluating a tendency in the presence or absence of an individual drug sensitivity, comprising a gene polymorphism of a cyclic AMP responsive element binding protein gene or a haplotype constituted by the gene polymorphism. 
     
     
         19 . A gene polymorphism marker for evaluating a tendency in the presence or absence of an individual disease vulnerability, comprising a gene polymorphism of a cyclic AMP responsive element binding protein gene or a haplotype constituted by the gene polymorphism.