PCSK9, LPL, APOE, eNOS, MTHFR Gene Polymorphisms and Myocardial Infarction Risk in Russians

Purpose: The aim of the present study was to analyze the association of polymorphous loci in the following genes: proprotein convertase subtilisin/kexin type 9 (PCSK9), lipoprotein lipase (LPL), apolipoprotein E (APOE), endothelial nitric oxide synthesis (eNOS) and methylenetetrahydrofolate reductase (MTHFR) with the risk of myocardial infarction (MI) in ethnic Russians.
Methods: This study included 405 unrelated patients with MI and 198 unrelated control subjects. We performed comparison of allelic and genotypic frequencies of APOE epsilon polymorphism (rs7412, rs429358) and single-nucleotide polymorphisms (SNPs) eNOS*−786T>C (rs2070744), LPL*495T>G (rs320), MTHFR*677C>T (rs1801133) and PCSK9*1420A>G (rs562556) in these groups. SNP genotyping of APOE, LPL, eNOS and MTHFR was performed using PCR - restriction fragment length polymorphism analysis. For PCSK9 genotyping, real-time PCR with pre-designed Applied Biosystems kits was used. All SNPs in the control group were in Hardy–Weinberg equilibrium (p > 0.01), as measured by Haploview 5.0 software. The APSampler algorithm was used to identify the alleles, genotypes and their combinations whose carriage was associated with MI.
Results: The frequencies of the genotypes PCSK9* 1420A/A, LPL*495G/G and APOE*ε3/ε3 were significantly higher in the group of patients with MI than in controls (p = 0.013, OR = 1.45, 95% CI: 1.00-2.10; p=0.032, OR=1.96, 95% CI: 1.00-3.91 and p = 0.034, OR = 1.52, 95% CI: 1.05-2.20, correspondingly). The carriage of eNOS*786C allele (the sum of genotypes C/C and C/T) was associated with MI (p = 0.0034, OR = 1.63, 95% CI: 1.16-2.30). No significant differences were found in allele/genotype carriage frequencies of SNP MTHFR* 677C>T in compared groups of patients with MI and healthy individuals. The biallelic sets of identified genetic variants were found, which are characterized by the higher significance of association with MI than each variant itself. Multiple logistic regression analysis was performed for the four genetic markers. The composite predictive model including these markers demonstrated a rather moderate area under the curve (AUC) of 0.60.
Conclusion: The carriage of PCSK9*1420А/А, LPL*495G/G, АPOЕ*ε3/ε3 genotypes and eNOS*786C allele are associated with MI in Russians.

This work was supported by the Russian Science Foundation (project 16-14-10251)