PCSK9 rs11591147 polymorphism and response to atorvastatin in patients with type 2 diabetes mellitus and/or hypertension

Background: The loss-of-function (LOF) variant rs11591147 of PCSK9 reduces PCSK9 activity and is expected to lower low-density lipoprotein cholesterol (LDL-C) and improve the response to statins, meaning a greater LDL-C reduction. However, studies are few and inconsistent. This study explored the association of the LOF variant with baseline lipid levels and the response to atorvastatin in statin-naïve patients. Methods: Eligible patients with type 2 diabetes mellitus and/or hypertension from two tertiary care hospitals in Delhi (n=260) received atorvastatin for 10–12 weeks. The PCSK9 rs11591147 polymorphism was studied by PCR-restriction fragment length polymorphism (PCR-RFLP) and the lipid profile, including LDL-C, was measured before and after treatment. Results: The frequency of the LOF T allele was 16.5%, with genotype frequencies of GG 66.9%, GT 33.1% and TT 0%. Baseline LDL-C was similar in both groups (GG 136.04±43.89 vs. GT 134.79±41.38 mg/dl; p=0.813), as was the percentage fall in LDL-C after atorvastatin (GG 28.7% vs. GT 26.9%; p=0.386). Genotype distribution deviated from Hardy–Weinberg equilibrium (p=0.001). Conclusions: In this North Indian cohort, the LOF T allele was not associated with baseline LDL-C or with the response to atorvastatin. Larger studies, including TT homozygotes, are needed to confirm these findings.