US2010056384A1PendingUtilityA1

Sequence Variations in PNPLA3 Associated with Hepatic Steatosis

Assignee: UNIV TEXASPriority: Sep 4, 2008Filed: Sep 3, 2009Published: Mar 4, 2010
Est. expirySep 4, 2028(~2.1 yrs left)· nominal 20-yr term from priority
C12Q 2600/172C12Q 2600/156C12Q 1/6883
66
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Claims

Abstract

Disclosed are methods of identifying a genetic variant in a person determined to have or be predisposed having a fatty liver by determining whether the person has PNPLA3-I148M. Also disclosed are methods of identifying a genetic variant in a person by determining whether the person has PNPLA3-I148M; and prescribing to the person a treatment to reduce liver fat or associated inflammation.

Claims

exact text as granted — not AI-modified
1 . A method of identifying a genetic variant in a person determined to have or be predisposed to having a liver disease selected from fatty liver, an increase in hepatic fat, hepatic steatosis, nonalcoholic fatty liver disease, and associated inflammation, the method comprising:
 (a) determining whether the person has PNPLA3-I148M.   
   
   
       2 . The method of  claim 1  further comprising the step of (b) determining whether the person has PNPLA3-S453I. 
   
   
       3 . The method of  claim 1  wherein the determining step (a) comprises detecting using a method selected from the group consisting of: mass spectroscopy, oligonucleotide microarray analysis, allele-specific hybridization, allele-specific PCR, and sequencing, a marker of PNPLA3-I148M that is SNP rs738408, or a surrogate SNP in linkage disequilibrium with the PNPLA3-I148M and having a r 2  value greater than 0.5, wherein the surrogate SNP is selected from: 
     
       
         
               
               
               
               
               
             
                   
                   
               
                   
                 rs12483959, 
                 rs1977081, 
                 rs2072905, 
                 rs1010022, 
               
                   
                 rs11090617, 
                 rs1883349, 
                 rs2896019, 
                 rs926633, 
               
                   
                 rs4823173, 
                 rs2281135, 
                 rs2073081, 
                 rs2294916, and 
               
                   
                 rs2076211, 
                 rs2072907, 
                 rs1010023, 
                 rs4823179. 
               
                   
                   
               
           
              
             
             
              
              
              
              
              
             
          
         
       
     
   
   
       4 . The method of  claim 2  wherein the determining step (a) comprises detecting using a method selected from the group consisting of: mass spectroscopy, oligonucleotide microarray analysis, allele-specific hybridization, allele-specific PCR, and sequencing, a marker of PNPLA3-I148M that is SNP rs738408, or a surrogate SNP in linkage disequilibrium with the PNPLA3-I148M and having a r 2  value greater than 0.5, wherein the surrogate SNP is selected from: 
     
       
         
               
               
               
               
               
             
                   
                   
               
                   
                 rs12483959, 
                 rs1977081, 
                 rs2072905, 
                 rs1010022, 
               
                   
                 rs11090617, 
                 rs1883349, 
                 rs2896019, 
                 rs926633, 
               
                   
                 rs4823173, 
                 rs2281135, 
                 rs2073081, 
                 rs2294916, and 
               
                   
                 rs2076211, 
                 rs2072907, 
                 rs1010023, 
                 rs4823179. 
               
                   
                   
               
           
              
             
             
              
              
              
              
              
             
          
         
       
     
   
   
       5 . The method of  claim 3  wherein the determining step (a) comprises detecting a plurality of the SNP and surrogate SNP markers. 
   
   
       6 . The method of  claim 4  wherein the determining step (a) comprises detecting a plurality of the SNP and surrogate SNP markers. 
   
   
       7 . A method of identifying a genetic variant in a person, the method comprising:
 (a) determining whether the person has PNPLA3-I148M; and   (b)(i) providing the person with information about risk of developing a liver disease selected from fatty liver, an increase in hepatic fat, hepatic steatosis, nonalcoholic fatty liver disease, and associated inflammation, or   (ii) providing the person with a recommendation for an additional diagnostic test or monitoring to detect an indication of the liver disease, or   (iii) prescribing to the person a treatment for the liver disease.   
   
   
       8 . The method of  claim 7  further comprising the step of (c) determining whether the person has PNPLA3-S453I. 
   
   
       9 . The method of  claim 7  wherein the determining step (a) comprises detecting using a method selected from the group consisting of: mass spectroscopy, oligonucleotide microarray analysis, allele-specific hybridization, allele-specific PCR, and sequencing, a marker of PNPLA3-I148M that is SNP rs738408, or a surrogate SNP in linkage disequilibrium with the PNPLA3-I148M and having a r 2  value greater than 0.5, wherein the surrogate SNP is selected from: 
     
       
         
               
               
               
               
               
             
                   
                   
               
                   
                 rs12483959, 
                 rs1977081, 
                 rs2072905, 
                 rs1010022, 
               
                   
                 rs11090617, 
                 rs1883349, 
                 rs2896019, 
                 rs926633, 
               
                   
                 rs4823173, 
                 rs2281135, 
                 rs2073081, 
                 rs2294916, and 
               
                   
                 rs2076211, 
                 rs2072907, 
                 rs1010023, 
                 rs4823179. 
               
                   
                   
               
           
              
             
             
              
              
              
              
              
             
          
         
       
     
   
   
       10 . The method of  claim 8  wherein the determining step (a) comprises detecting using a method selected from the group consisting of: mass spectroscopy, oligonucleotide microarray analysis, allele-specific hybridization, allele-specific PCR, and sequencing, a marker of PNPLA3-I148M that is SNP rs738408, or a surrogate SNP in linkage disequilibrium with the PNPLA3-I148M and having a r 2  value greater than 0.5, wherein the surrogate SNP is selected from: 
     
       
         
               
               
               
               
               
             
                   
                   
               
                   
                 rs12483959, 
                 rs1977081, 
                 rs2072905, 
                 rs1010022, 
               
                   
                 rs11090617, 
                 rs1883349, 
                 rs2896019, 
                 rs926633, 
               
                   
                 rs4823173, 
                 rs2281135, 
                 rs2073081, 
                 rs2294916, and 
               
                   
                 rs2076211, 
                 rs2072907, 
                 rs1010023, 
                 rs4823179. 
               
                   
                   
               
           
              
             
             
              
              
              
              
              
             
          
         
       
     
   
   
       11 . The method of  claim 9  wherein the determining step comprises detecting a plurality of the SNP and surrogate SNP markers. 
   
   
       12 . The method of  claim 10  wherein the determining step comprises detecting a plurality of the SNP and surrogate SNP markers. 
   
   
       13 . A method of identifying a genetic variant in a person determined to have or be predisposed to having a subnormal hepatic fat or triglyceride content, or a subnormal susceptibility to hepatic steatosis or nonalcoholic fatty liver disease, the method comprising:
 determining whether the person has PNPLA3-S4531.   
   
   
       14 . The method of  claim 13  wherein the determining step comprises detecting using a method selected from the group consisting of: mass spectroscopy, oligonucleotide microarray analysis, allele-specific hybridization, allele-specific PCR, and sequencing, a marker of PNPLA3-S453I that is SNP rs6006460, or a surrogate SNP in linkage disequilibrium with the PNPLA3-S453I and having a r 2  value greater than 0.5. 
   
   
       15 . The method of  claim 13  wherein the determining step comprises detecting a plurality of the SNP and surrogate SNP markers. 
   
   
       16 . A method of identifying a genetic variant in a person, the method comprising:
 determining whether the person has PNPLA3-S453I; and   providing the person with information about predisposition to have a subnormal hepatic fat or triglyceride content or a subnormal susceptibility to hepatic steatosis or nonalcoholic fatty liver disease, or providing the person with a recommendation for an additional diagnostic test or monitoring to detect an indication of liver disease, or prescribing to the person an alternative treatment for liver disease.   
   
   
       17 . The method of  claim 16  wherein the determining step comprises detecting using a method selected from the group consisting of: mass spectroscopy, oligonucleotide microarray analysis, allele-specific hybridization, allele-specific PCR, and sequencing, a marker of PNPLA3-S453I that is SNP r s6006460, or a surrogate SNP in linkage disequilibrium with the PNPLA3-S453I and having a r 2  value greater than 0.5. 
   
   
       18 . The method of  claim 16  wherein the determining step comprises detecting a plurality of the SNP and surrogate SNP markers.

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