Diagnostic methods

Abstract

This invention relates to a method of determining the susceptibility of an individual to statin-induced myopathy, comprising detecting the presence or absence of one or more polymorphisms in the SLCO1B1 gene in a biological sample from an individual, whereby the presence of one or more polymorphisms indicates that the individual has altered susceptibility to statin-induced myopathy.

1 . A method of determining the susceptibility of an individual to statin-induced myopathy, comprising detecting the presence or absence of one or more polymorphisms in the SLCO1B1 gene in a biological sample from an individual, whereby the presence of one or more polymorphisms indicates that the individual has an altered susceptibility to statin-induced myopathy. 
     
     
         2 . A method of reducing the risk of myopathy in an individual during treatment with a statin, comprising
 i) detecting the presence or absence of one or more polymorphisms in the SLCO1B1 gene in a biological sample from an individual;   ii) classifying the individual according to their susceptibility to statin-induced myopathy, by reference to the presence or absence of the one or more polymorphisms detected in step i); and   iii) determining a suitable dosage for statin treatment by reference to the susceptibility of the individual to statin-induced myopathy determined in step ii).   
     
     
         3 . The method as claimed in  claim 1 , wherein the one or more polymorphisms are selected from the SNP rs4149056 and/or a polymorphism in close linkage with rs4149056. 
     
     
         4 . The method as claimed in  claim 3 , wherein the method comprises determining whether the individual has a homozygous or heterozygous genotype for a cytosine (C) or a thymine (T) at rs4149056. 
     
     
         5 . The method as claimed in  claim 3 , wherein the one or more polymorphisms in close linkage with rs4149056 are selected from the group consisting of rs4363657, rs1871395, rs12317268, rs2900478, rs4149100, rs4149081, rs11045879, rs7969341, rs11045885, rs12369881, and rs12366582. 
     
     
         6 . A method of determining a suitable dosage for an individual in need of treatment with a statin, comprising
 i) determining whether the genotype of the individual is heterozygous or homozygous for one or more polymorphisms in the SLCO1B1 gene in a biological sample from an individual; and   ii) determining a suitable dosage for statin treatment by reference to the genotype of the one or more polymorphisms, whereby a standard dose of a statin is suitable for an individual with a heterozygous or homozygous high-risk genotype and a higher dose is suitable for an individual with a homozygous low-risk genotype.   
     
     
         7 . A method of treating an individual in need of treatment with a statin, comprising
 i) determining whether the genotype of the individual is heterozygous or homozygous for one or more polymorphisms in the SLCO1B1 gene in a biological sample from an individual;   ii) classifying the individual according to their genotype at the one or more polymorphisms as determined in step i); and   iii) administering a dose of a statin, whereby a standard dose of a statin is suitable for an individual with a heterozygous or homozygous high-risk genotype and a higher dose is suitable for an individual with a homozygous low-risk genotype.   
     
     
         8 . The method as claimed in  claim 6 , wherein the one or more polymorphisms are selected from the SNP rs4149056 and/or a polymorphism in close linkage with rs4149056. 
     
     
         9 . The method as claimed in  claim 8 , wherein the method comprises determining whether the individual has a homozygous or heterozygous genotype for a cytosine (C) or a thymine (T) at rs4149056. 
     
     
         10 . The method as claimed in  claim 8 , wherein the one or more polymorphisms in close linkage with rs4149056 are selected from the group consisting of rs4363657, rs1871395, rs12317268, rs2900478, rs4149100, rs4149081, rs11045879, rs7969341, rs11045885, rs12369881, and rs12366582. 
     
     
         11 . The method as claimed in  claim 6 , wherein the one or more polymorphisms is SNP rs4149056, and wherein a standard dose of a statin is suitable for an individual with a CC or TC genotype, and a higher dose is suitable for an individual with a TT genotype. 
     
     
         12 . The method as claimed in  claim 11 , wherein the statin is simvastatin, and wherein a standard dose is 20 or 40 mg daily, and a higher dose is 80 mg daily. 
     
     
         13 . The method as claimed in  claim 6 , wherein the individual has an increased risk of myopathy due to the concomitant use of drugs that slow statin clearance, or due to the decreased hepatic uptake or renal clearance of statins due to genetic variants or disease. 
     
     
         14 . An in-vitro diagnostic kit for screening for susceptibility of an individual to statin-induced myopathy, comprising one or more reagents for detecting the presence or absence of one or more polymorphisms in the SLCO1B1 gene in a biological sample from an individual. 
     
     
         15 . The kit as claimed in  claim 14 , wherein the one or more reagents comprise allele-specific amplification primers and/or allele-specific probes capable of determining whether the genotype of the individual is heterozygous or homozygous for a cytosine (C) or a thymine (T) at the SNP rs4149056. 
     
     
         16 . The kit as claimed in  claim 15 , wherein the kit comprises instructions for use which define a suitable dosage for statin treatment by reference to the rs4149056 genotype of the individual, whereby a standard dose of a statin is suitable for an individual with a CC or TC genotype and a higher dose is suitable for an individual with a TT genotype. 
     
     
         17 . The method as claimed in  claim 2 , wherein the one or more polymorphisms are selected from the SNP rs4149056 and/or a polymorphism in close linkage with rs4149056. 
     
     
         18 . The method as claimed in  claim 17 , wherein the method comprises determining whether the individual has a homozygous or heterozygous genotype for a cytosine (C) or a thymine (T) at rs4149056. 
     
     
         19 . The method as claimed in  claim 17 , wherein the one or more polymorphisms in close linkage with rs4149056 are selected from the group consisting of rs4363657, rs1871395, rs12317268, rs2900478, rs4149100, rs4149081, rs11045879, rs7969341, rs11045885, rs12369881, and rs12366582. 
     
     
         20 . The method as claimed in  claim 7 , wherein the one or more polymorphisms are selected from the SNP rs4149056 and/or a polymorphism in close linkage with rs4149056. 
     
     
         21 . The method as claimed in  claim 20 , wherein the method comprises determining whether the individual has a homozygous or heterozygous genotype for a cytosine (C) or a thymine (T) at rs4149056. 
     
     
         22 . The method as claimed in  claim 20 , wherein the one or more polymorphisms in close linkage with rs4149056 are selected from the group consisting of rs4363657, rs1871395, rs12317268, rs2900478, rs4149100, rs4149081, rs11045879, rs7969341, rs11045885, rs12369881, and rs12366582. 
     
     
         23 . The method as claimed in  claim 7 , wherein the one or more polymorphisms is SNP rs4149056, and wherein a standard dose of a statin is suitable for an individual with a CC or TC genotype, and a higher dose is suitable for an individual with a TT genotype. 
     
     
         24 . The method as claimed in  claim 23 , wherein the statin is simvastatin, and wherein a standard dose is 20 or 40 mg daily, and a higher dose is 80 mg daily. 
     
     
         25 . The method as claimed in  claim 7 , wherein the individual has an increased risk of myopathy due to the concomitant use of drugs that slow statin clearance, or due to the decreased hepatic uptake or renal clearance of statins due to genetic variants or disease.