Estrogen receptor alleles that are predictive of increased susceptibility to bone fracture

Abstract

In one aspect, the present invention provides methods of determining susceptibility to bone fracture in a mammalian subject, wherein the methods comprise analyzing nucleic acid molecules obtained from the mammalian subject to determine which of the P, p X, and x alleles of the estrogen receptor α gene are present, wherein the presence of a haplotype comprising the p and x alleles is indicative of an increased susceptibility to bone fracture. The present invention also provides kits for determining susceptibility to bone fracture in a mammalian subject.

1 - 26 . (canceled) 
     
     
         27 . A kit for determining susceptibility to bone fracture in a mammalian subject, said kit comprising (i) one or more nucleic acid primer molecules for amplification of a portion of an estrogen receptor α gene, (ii) means for determining whether a px haplotype of said gene is present; and (iii) means for indicating a correlation between the presence of said haplotype and risk of bone fracture. 
     
     
         28 . A kit according to  claim 27 , said kit further comprising (i) one or more nucleic acid primer molecules for amplification of a portion of a vitamin D receptor gene, (ii) means for determining whether a baT haplotype of the vitamin D receptor gene is present, and (iii) means for indicating a correlation between the presence of the baT haplotype and risk of bone fracture. 
     
     
         29 - 30 . (canceled) 
     
     
         31 . A method for providing a treatment regimen to an individual, comprising determining the estrogen receptor α gene haplotype of the P/p and X/x alleles and providing a treatment regimen to decrease the risk of bone fracture when the individual has haplotype 1 (px) of the estrogen receptor α gene. 
     
     
         32 . The method of  claim 31 , wherein the individual is homozygous for haplotype 1 (px). 
     
     
         33 . The method of  claim 31 , wherein the treatment comprises at least one treatment selected from the group consisting of modifications to lifestyle, regular exercise, changes in diet and administration of a pharmaceutical preparation effective to prevent or reduce the risk of vertebral BMD-independent fracture. 
     
     
         34 . The method of  claim 33 , wherein the pharmaceutical preparation is selected from the group consisting of vitamin D preparations and calcium supplements. 
     
     
         35 . The method of  claim 31 , wherein the individual is a Caucasian female. 
     
     
         36 . A method for providing a treatment regimen to an individual, comprising determining the estrogen receptor α gene haplotype of the P/p and X/x alleles;
 determining the vitamin D receptor gene haplotype of the B/b, A/a and T/t alleles; and 
 providing a treatment regimen to decrease the risk of bone fracture when the individual has haplotype 1 (px) of the estrogen receptor α gene and is homozygous for haplotype 1 (baT) of the vitamin D receptor gene. 
 
     
     
         37 . The method of  claim 36 , wherein the individual is homozygous for haplotype 1 (px). 
     
     
         38 . The method of  claim 36 , wherein the treatment comprises at least one treatment selected from the group consisting of modifications to lifestyle, regular exercise, changes in diet and administration of a pharmaceutical preparation effective to prevent or reduce the risk of vertebral BMD-independent fracture. 
     
     
         39 . The method of  claim 38 , wherein the pharmaceutical preparation is selected from the group consisting of vitamin D preparations and calcium supplements 
     
     
         40 . The method of  claim 36 , wherein the individual is a Caucasian female. 
     
     
         41 . A method for predicting the response of a mammalian subject to treatment to decrease the risk of vertebral bone fracture that comprises:
 determining the estrogen receptor α gene haplotype of the P/p and X/x alleles;   determining the vitamin D receptor gene haplotype of the B/b, A/a and T/t alleles; and predicting a greater response to treatment when the individual has estrogen receptor α gene haplotype 1 (px) and is homozygous for vitamin D receptor gene haplotype 1 (baT).   
     
     
         42 . The method of  claim 41 , wherein the individual is homozygous for haplotype 1 (px). 
     
     
         43 . A method for providing a treatment regimen to an individual, comprising determining the estrogen receptor α gene haplotype of the P/p and X/x alleles and providing a treatment regimen to increase lumbar bone mineral density when the individual has haplotype 1 (px) of the estrogen receptor α gene. 
     
     
         44 . The method of  claim 43 , wherein the individual is homozygous for haplotype 1 (px).