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

• Main Authors: Gilberto Vargas-Alarcón, Oscar Pérez-Méndez, Héctor González-Pacheco, Julián Ramírez-Bello, Rosalinda Posadas-Sánchez, Galileo Escobedo, José Manuel Fragoso
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: Cells
• Subjects: genetics; susceptibility; acute coronary syndrome; proprotein convertase subtilisin–kexin type 7
• Online Access: https://www.mdpi.com/2073-4409/10/6/1444

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 <i>(PCSK7)</i> gene are associated with plasma lipid levels. In the present study, we evaluated whether <i>PCSK7</i> gene polymorphisms are significantly associated with the plasma lipid profile and ACS. Three <i>PCSK7</i> gene polymorphisms (rs508487 <i>T</i>/<i>C</i>, rs236911 <i>C</i>/<i>A,</i> and rs236918 <i>C</i>/<i>G</i>) 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 <i>C</i> allele was associated with a high risk of ACS (OR = 2.11, <i>pC</i> = 0.039). In the same way, under the recessive and additive models, the rs236911 <i>C</i> allele was associated with a high risk of ACS (OR = 1.95, <i>pC</i> = 0.037, and OR = 1.28, <i>pC</i> = 0.037, respectively). In addition, under the co-dominant model, the rs508487 <i>T</i> allele was associated with a higher risk of ACS (OR = 1.78, <i>pC</i> = 0.010). The <i>CCC</i> and <i>TCC</i> haplotypes were associated with a high risk of ACS (OR = 1.21, <i>pC</i> = 0.047, and OR = 1.80, <i>pC</i> = 0.001, respectively). The rs236911 <i>CC</i> and rs236918 <i>CC</i> genotypes were associated with lower high-density lipoproteins-cholesterol (HDL-C) plasma concentrations, whereas the rs236911 <i>CC</i> 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 <i>PCSK7</i> rs508487 <i>T</i>/<i>C</i>, rs236911 <i>C</i>/<i>A,</i> and rs236918 <i>C</i>/<i>G</i> polymorphisms are associated with the risk of developing ACS, and with plasma concentrations of HDL-C and triglycerides.