Genetic determinants of lipid-lowering response to atorvastatin therapy in an Indian population

• Published in: Journal of clinical pharmacy and therapeutics Vol. 41; no. 3; pp. 329 - 333
• Main Authors: Kadam, P., Ashavaid, T. F., Ponde, C. K., Rajani, R. M.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.06.2016; Hindawi Limited
• Subjects: Aged; Alleles; atorvastatin; Atorvastatin Calcium - pharmacology; Atorvastatin Calcium - therapeutic use; Cholesterol, LDL - blood; Female; Genetic Variation; Genotype; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypercholesterolemia - drug therapy; India; low-density lipoprotein-cholesterol; Male; Middle Aged; Pharmacogenetics; Polymorphism, Single Nucleotide; polymorphisms; Treatment Outcome; atorvastatin; polymorphisms; pharmacogenetics; low-density lipoprotein-cholesterol
• ISSN: 0269-4727; 1365-2710
• DOI: 10.1111/jcpt.12369

Summary 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. Genetic variations in CYP7A1, CYP3A4, SLCO1B1 and ABCB1 are associated with the variable response to atorvastatin therapy in terms of LDL‐cholesterol lowering.