Association between genetic polymorphisms and other attributing factors with lipid profiles among statin users: a cross-sectional retrospective study

Abstract

Background: Statins are well known for their efficacy to improve lipid profiles. Their efficacy varies between individuals and can be modified by patient factors such as genetic polymorphisms. This study used a cross-sectional retrospective design to assess the effect of selected single nucleotide polymorphisms (SNPs) and other patient-specific clinical variables on statin-related lipid profile changes in a subgroup of Malaysians. The impact of low and moderate intensity of statin doses (10–40 mg/day for at least six weeks), regardless of statin types, was assessed between SNPs of previously identified genes with clinical relation to statin efficacy and lipid profile changes before (baseline) and after statin treatment; two ranges of treatment durations, i.e. ≤ 6 months and 7–12 months. DNA was extracted from patient's venous blood (3 mL), and SNP genotyping was performed using PCR–RFLP method. Using a dominant genetic model, the association between selected SNPs from six genes of interest (ABCG2, ABCC2, APOE, APOA5, GATM and COQ2) and the patients' lipid profiles was investigated. Results: A total of 229 statin-treated patients were included. The mean age of the patients was 53 ± 7.16 years, and they were mostly females (53.3%), Malay (96.1%), and were taking atorvastatin and simvastatin (90.4%). Seven SNPs genotyped from six genes investigated were related to different lipid profile before and after statin treatment. At baseline, ABCG2 rs2231142 (P = 0.035) and APOA5 rs662799 (P = 0.007) variants had higher HDL-c levels, while ABCC2 rs717620 variants had higher TC (P = 0.040) and LDL-c levels (P = 0.022). Following statin treatment, ABCC2 rs717620 (lower TG, P = 0.009) and APOA5 rs662799 (higher HDL, P = 0.031; lower TG, P = 0.037) were associated with improved lipid profiles, with the association being substantially related to males carrying minor alleles of the SNPs. None of the investigated SNPs were related to significant statin-related LDL-c lowering effects during statin therapy. Conclusion: To better understand inter-individual heterogeneity in lipid profiles during statin therapy, it would be helpful to take patient genetics and gender into consideration before and after administering statins.