The rs508487, rs236911, and rs236918 Genetic Variants of the Proprotein Convertase Subtilisin-Kexin Type 7 (PCSK7) Gene Are Associated with Acute Coronary Syndrome and with Plasma Concentrations of HDL-Cholesterol and Triglycerides.

Gilberto Vargas-Alarcón,Héctor González-Pacheco,Julián Ramírez-Bello,Oscar Pérez-Méndez,Galileo Escobedo,Rosalinda Posadas-Sánchez,José Manuel Fragoso

doi:10.3390/cells10061444

Abstract

Dyslipidemia has a substantial role in the development of acute coronary syndrome (ACS). Previous reports, including genome-wide associations studies (GWAS), have shown that some genetic variants of the proprotein convertase subtilisin–kexin type 7 (PCSK7) gene are associated with plasma lipid levels. In the present study, we evaluated whether PCSK7 gene polymorphisms are significantly associated with the plasma lipid profile and ACS. Three PCSK7 gene polymorphisms (rs508487 T/C, rs236911 C/A, and rs236918 C/G) were determined using TaqMan genotyping assays in a group of 603 ACS patients and 622 healthy controls. The plasma lipid profile was determined in the study groups by enzymatic/colorimetric assays. Under the recessive model, the rs236918 C allele was associated with a high risk of ACS (OR = 2.11, pC = 0.039). In the same way, under the recessive and additive models, the rs236911 C allele was associated with a high risk of ACS (OR = 1.95, pC = 0.037, and OR = 1.28, pC = 0.037, respectively). In addition, under the co-dominant model, the rs508487 T allele was associated with a higher risk of ACS (OR = 1.78, pC = 0.010). The CCC and TCC haplotypes were associated with a high risk of ACS (OR = 1.21, pC = 0.047, and OR = 1.80, pC = 0.001, respectively). The rs236911 CC and rs236918 CC genotypes were associated with lower high-density lipoproteins-cholesterol (HDL-C) plasma concentrations, whereas the rs236911 CC genotype was associated with a higher concentration of triglycerides, as demonstrated in the control individuals who were not receiving antidyslipidemic drugs. Our data suggest that the PCSK7 rs508487 T/C, rs236911 C/A, and rs236918 C/G polymorphisms are associated with the risk of developing ACS, and with plasma concentrations of HDL-C and triglycerides.

Highlights

acute coronary syndrome (ACS) is a complex multifactorial disorder resulting from genetics and various environmental factors, coupled with dyslipidemias, hypertension, diabetes, obesity, and a smoking habit—factors that play a fundamental role in the development and progression of atherosclerosis [1,2,3]
We reported the association of the rs508487 T, rs236911 C, and rs236918 C alleles with the risk of developing ACS
Kurano et al reported in a Genome-wide association studies (GWAS) that the rs508487 T and rs236911 C alleles were associated with the risk of hypertriglyceridemia in the Japan Pharmacogenomics Data Science Consortium (JPDSC) [13]

Summary

Introduction

ACS is a complex multifactorial disorder resulting from genetics and various environmental factors, coupled with dyslipidemias, hypertension, diabetes, obesity, and a smoking habit—factors that play a fundamental role in the development and progression of atherosclerosis [1,2,3]. Recent studies have shown that the human PCSK7 proprotein is implicated in the regulation of apolipoprotein A-5 (apoA-5) and is associated with a higher triglyceride concentration [6,7], both with an important role in the development of cardiovascular diseases [3,8,9,10]. Recent studies have associated three novel SNPs [PCSK7 nearGene-3 rs508487 T/C, PCSK7 intron 6 rs236911 C/A, and PCSK7 intron 9 rs236918 C/G] with an overexpression of the PCSK7 and hypertriglyceridemia [6,10,11,12,13], as well as with the risk of developing atherosclerosis and liver disease [4,10]

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Conclusion