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.
Highlights
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
Our study provides the first evidence that PCSK9 gene polymorphisms may serve as independent prognostic markers for MI patients in Iran
Summary
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. Myocardial infarction (MI) is a leading cause of global mortality and the most prevalent subgroup of coronary heart diseases (CHDs).[1,2] Among significant risk factors of MI are smoking, hypertension, diabetes mellitus, obesity, and low-density lipoprotein (LDL) and triglyceride (TG) levels.[3,4] Family history, age, and gender are characterized as non-modifiable risk factors.[4] Beside the inevitable role of non-genetic factors in predisposition to MI, higher concordance in monozygotic twins and increase in the incidence of MI in cases with positive family history highlight the footsteps of the genetics in MI etiology.[5] During years, linkage analyses and genome-wide association studies concluded in a huge list of genes and single nucleotide polymorphisms (SNPs) for their potential role in MI pathogenesis.[6,7,8,9,10] Among these, the genes involved in cholesterol homeostasis pathway, including Apo-lipoprotein B-100 (APOB-100),[11] LDL receptor (LDLR),[12] proprotein convertase subtilisin/kexin type 9 (PCSK9),[13,14] and oxidized low-density lipoprotein receptor 1 (OLR1),[14] seem the best candidates for their contribution in CHDs
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