PCSK9 Gene Polymorphisms Associated With the Risk of Myocardial Infarction in Iranian Patients

Abstract

Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulatory protein in lipid metabolism and a candidate gene in the etiology of cardiovascular diseases. The present study aimed to evaluate the prevalence and significance of PCSK9 rs505151 and rs11591147 variants with myocardial infarction (MI) risk in the Iranian population. Patients and Methods: The frequency of the PCSK9 rs505151 and rs11591147 variants were compared between 600 cases of MI and 600 healthy age- and sex-matched individuals. Tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS PCR) was used for rs505151, and amplification refractory mutation system-polymerase chain (ARMS-PCR) was utilized to detect the rs11591147 polymorphism. Finally, SPSS and SHEsis software were applied for data analysis. Results: Carriers of the GG genotype of rs505151 polymorphism (OR: 1.57, 95% CI: 1.05–2.35, P = 0.02; age-adjusted; OR: 1.54, 95% CI: 1.03–2.32, P = 0.03) and at least one G-allele including GG+AG vs. AA (OR: 1.54, 95% CI: 1.04–2.28, P = 0.03; age-adjusted; OR: 1.51, 95% CI: 1.01–2.24, P = 0.04) have an increased risk of MI. No association between PCSK9 rs505151 alleles and MI risk was observed. The ratio of individuals with the rs11591147GT variant was higher in healthy individuals vs. patients with MI (48.6% vs. 41.7%), indicating a reduced risk of developing MI (OR: 0.75; 95% CI: 0.59–0.95; P = 0.01; age-adjusted; OR: 0.74; 95% CI: 0.58–0.95; P = 0.01). The carriers of at least one T allele (TT+GT vs. GG) (OR: 0.78; 95% CI: 0.62–0.98; P = 0.03; age-adjusted; OR: 0.78; 95% CI: 0.62–0.98; P = 0.03) showed a significant reduction in MI risk. The allelic frequencies at this polymorphic site did not differ between MI patients and healthy counterparts. No association was found between the haplotypes constructed from the alleles of these two polymorphisms. Conclusion: Our study provides the first evidence that PCSK9 gene polymorphisms may serve as independent prognostic markers for MI patients in Iran.