Compositions and methods for treating and preventing coronary heart disease

Abstract

The invention pertains to a method of determining a statin dosage for an individual in need of treatment with a statin, comprising determining a SLCO1B1 genotype from a nucleic acid sample of the individual, said genotype comprising the presence or absence of the SLCO1B1-056 polymorphism, and determining an ApoE genotype or phenotype identifying an ApoE polymorphism selected from the group consisting of ApoE2, ApoE3, ApoE4, and any combination thereof, wherein the combination of a SLCO1B1 genotype identifying the presence of the SLCO1B1-056 C polymorphism and the ApoE genotype or phenotype identifying one of the ApoE3/4 or ApoE4/4 genotypes indicates the statin dosage.

We claim: 
     
         1 . A method of determining a statin dosage, the method comprising the steps of:
 conducting an assay in a biological sample to identify the presence or absence of a SLCO1B1 biomarker and an Apolipoprotein E gene (ApoE) biomarker that are associated with statin efficacy; and   determining a dosage of statin for the individual based upon the presence or absence of the SLCO1B1 and ApoE biomarkers, wherein the statin is selected from the group consisting of pravastatin, atorvastatin, and cerivastatin.   
     
     
         2 . The method of  claim 1 , wherein the biomarkers are genetic polymorphisms. 
     
     
         3 . The method of  claim 2 , wherein the polymorphisms comprise an rs4149056 C polymorphism at a SLCO1B1 locus and selected from the group consisting of an ApoE2 polymorphism, an APoE3 polymorphism, and an ApoE4 polymorphism at an ApoE locus. 
     
     
         4 . The method of  claim 2 , wherein the polymorphisms comprise a C/T or a T/T genotype at SLCO1B1-056 and an ApoE genotype selected from the group consisting of ApoE2/E2, ApoE2/E3, and ApoE3/E3. 
     
     
         5 . The method of  claim 4 , wherein the statin dosage is between about 20 and about 40 milligrams. 
     
     
         6 . The method of  claim 1 , further comprising the step of measuring an amount of the biomarker. 
     
     
         7 . The method of  claim 6 , wherein the level and the amount are weighted. 
     
     
         8 . A method for identifying a patient's likelihood of responding to statin treatment, the method comprising the steps of:
 identifying a SLCO1B1 polymorphism and an ApoE polymorphism in a blood and/or plasma sample obtained from a patient, the SLCO1B1 and ApoE polymorpohisms being indicative of statin efficacy;   characterizing the patient's likelihood of responding to statin treatment based upon the presence or absence of the SLCO1B1 and ApoE polymorphisms identified in the identifying step, wherein the statin treatment comprises a statin selected from the group consisting of pravastatin, atorvastatin, and cerivastatin.   
     
     
         9 . The method of  claim 8 , further comprising categorizing the patient as a normal responder or a hypo-responder. 
     
     
         10 . The method of  claim 8 , further comprising the step of obtaining a plasma lathosterol/cholesterol ratio in the sample and wherein the characterizing step is further based upon the plasma lathosterol/cholesterol ratio. 
     
     
         11 . The method of  claim 10 , wherein the ratio and the polymorphisms contraindicate statin treatment. 
     
     
         12 . The method of  claim 11 , wherein the ratio is less than about 215. 
     
     
         13 . A diagnostic kit for determining a statin dosage for an individual, the diagnostic kit comprising:
 a first reagent for detecting the presence or absence of a SLCO1B1 biomarker in a biological sample from the individual; and   a second reagent for detecting the presence or absence of an Apolipoprotein E gene (ApoE) biomarker in the biological sample.   
     
     
         14 . The diagnostic kit of  claim 13 , wherein the biomarkers are genetic polymorphisms. 
     
     
         15 . The diagnostic kit of  claim 14 , wherein the polymorphisms comprise an rs4149056 C polymorphism at a SLCO1B1 locus and selected from the group consisting of an ApoE2 polymorphism, an APoE3 polymorphism, and an ApoE4 polymorphism at an ApoE locus. 
     
     
         16 . The diagnostic kit of  claim 14 , wherein the polymorphisms comprise a C/T or a T/T genotype at SLCO1B1-056 and an ApoE genotype selected from the group consisting of ApoE2/E2, ApoE2/E3, and ApoE3/E3.