Genetic determinants of lipid-lowering response to atorvastatin therapy in an Indian population.
WHAT IS KNOWN AND 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.


RESULTS AND DISCUSSION
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.


WHAT IS NEW AND CONCLUSION
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.
['Kadam|P|P|', 'Ashavaid|T F|TF|', 'Ponde|C K|CK|', 'Rajani|R M|RM|']
D000368:Aged D000483:Alleles D000069059:Atorvastatin D008078:Cholesterol, LDL D005260:Female D014644:Genetic Variation D005838:Genotype D006801:Humans D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors D006937:Hypercholesterolemia D007194:India D008297:Male D008875:Middle Aged D010597:Pharmacogenetics D020641:Polymorphism, Single Nucleotide D016896:Treatment Outcome
atorvastatin low-density lipoprotein-cholesterol polymorphisms pharmacogenetics