title: Genetic determinants of lipid-lowering response to atorvastatin therapy in an Indian population.
abstract: OBJECTIVE
  Statins form the backbone of lipid-lowering therapy for the prevention of cardiovascular disease. However, there is large interindividual variability in clinical response to statin treatment. Several gene variants that can be aligned to either the pharmacokinetics or pharmacodynamics of statin have been proposed as potentially important determinants of statin response. We aimed to study the association of known variations in SLCO1B1, CYP3A4, ABCB1, CYP3A5, ABCG5 and CYP7A1 genes with lipid levels in response to atorvastatin therapy.
  
  
  METHODS
  Genotypes were determined using multiplex allele-specific polymerase chain reaction in 177 Indian patients, treated with 10 mg of atorvastatin for 8 weeks. Low-density lipoprotein-cholesterol (LDL-C) levels were recorded at baseline and after 8 weeks of atorvastatin treatment.
  
  
  CONCLUSIONS
  A total of 177 hypercholesterolaemic patients were genotyped to study genetic determinants of atorvastatin response. The genotype distribution for all polymorphisms investigated was in Hardy-Weinberg equilibrium. In our study, patients with wild-type genotypes of CYP7A1 (rs3808607), CYP3A4 (rs2740574), SLCO1B1 (rs2306283) and variant allele-carrying genotype of ABCB1 (rs2032582, rs1045642) showed significantly greater LDL-cholesterol reductions in response to atorvastatin therapy.
  
  
  CONCLUSIONS
  The variable response to atorvastatin therapy in terms of LDL-cholesterol lowering due to genetic variations in CYP7A1, CYP3A4, SLCO1B1 and ABCB1 is a promising finding. Further validation in large Indian cohorts is required before it can be assessed for clinical utility.
authors.affiliation: Research Laboratories, P.D. Hinduja Hospital and Medical Research Centre, Mumbai, India.
authors.forename: P
authors.initials: P
authors.lastname: Kadam
authors.affiliation: Department of Laboratory Medicine and Laboratory Research, P.D. Hinduja Hospital and Medical Research Centre, Mumbai, India.
authors.forename: T F
authors.initials: TF
authors.lastname: Ashavaid
authors.affiliation: Cardiology, P.D. Hinduja Hospital and Medical Research Centre, Mumbai, India.
authors.forename: C K
authors.initials: CK
authors.lastname: Ponde
authors.affiliation: Cardiology, P.D. Hinduja Hospital and Medical Research Centre, Mumbai, India.
authors.forename: R M
authors.initials: RM
authors.lastname: Rajani
mesh_terms: D000368:Aged; D000483:Alleles; D000069059:Atorvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy*; D007194:India; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069059:Atorvastatin
keywords: atorvastatin; low-density lipoprotein-cholesterol; pharmacogenetics; polymorphisms