Polymorphic Assessment of the Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Variant Rs11591147 in Relation to Coronary Artery Disease in Pakistani Subjects

Polymorphic Assessment of the Proprotein Convertase Variant

Abstract

Coronary artery disease (CAD) is caused by the narrowing of coronary arteries because of plaque formation in response to multiple genetic and environmental factors. Many genetic markers associated with CAD susceptibility have been identified in extensive studies over the past few years. The enzyme proprotein convertase subtilisin/kexin type 9 (PCSK9) targets LDL receptors for degradation and decreases the clearance from the circulatory system of LDL cholesterol (LDLC). Loss-of-function mutations in the PCSK9 gene increase LDLC clearance, however. One such variant, rs11591147 (also known as G137T or R46L), is protective and more prevalent in White populations compared to other ethnic groups. The present study evaluated the allele and genotype frequencies of rs11591147 and investigated the effect of rs11591147 on CAD risk as well as its relationship with lipid levels in a Pakistani population. KASPar allelic discrimination assay was used to genotype 625 samples (405 CAD cases and 225 controls). Lipid profiles for the study participants were measured through spectrophotometric analysis. In CAD cases, the frequency of the risk allele (G) was slightly higher (0.999) than that in controls (0.995), albeit without a statistically significant difference (p=0.252). No association with CAD risk was observed (p=0.29). However, the SNP showed an impact on lipid levels, with each risk allele increasing LDLC by 14.81 ± 15.8 mg/dL and total cholesterol (TC) by 9.9 ± 30.4 mg/dL (mean ± SE). While this variant did not show a statistically significant association with CAD risk in the study, its effect direction aligns with observations in White populations. Future studies with larger sample sizes from all provinces of Pakistan and analysis of other PCSK9 variants are recommended to clarify the role of PCSK9 variants in CAD susceptibility.