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

Smita Tripathi; Ghan Shyam Pangtey; Animesh Ray; Subhradip Karmakar

doi:10.18203/2319-2003.ijbcp20263782

Authors

Smita Tripathi Department of Biochemistry, Lady Hardinge Medical College, New Delhi, India
Ghan Shyam Pangtey Department of Medicine, Lady Hardinge Medical College, New Delhi, India
Animesh Ray Department of Medicine, AIIMS, Delhi, India
Subhradip Karmakar Department of Biochemistry, AIIMS, Delhi, India

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20263782

Keywords:

Allele, Atorvastatin, Loss of function, LDL-C, PCR-RFLP, PCSK9, SNP, Statins

Abstract

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.

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