Search for Age-Dependent Genetic Risk Factors for Predicting Early Myocardial Infarction in Men And Women

Aim     To assess the association of polymorphic variants of candidate genes, including two miR-375 microRNA target genes (PRKCA and CDC42) and AGTR1, PAI1, IL10, IFNG, and TGFB1 genes involved in the pathogenesis of atherosclerosis as the major cause of myocardial infarction (MI), with the age of the first MI in groups of patients of different sexes.

Material and methods            Genotyping of DNA samples from peripheral blood of 548 ethnic Russian patients with a known age of MI onset was performed using real-time polymerase chain reaction. Differences in the frequencies of carriage of alleles and genotypes of the studied polymorphic variants, as well as their biallelic combinations, were analyzed in groups of patients with an age of MI onset less than and more than the median.

Results            In men, an association was found between the age of first MI and carriage of the AGTR1 rs5186*C / C (p=0.016; odds ratio, OR, 2.58; 95% confidence interval, CI: 1.13-5.89) and PRKCA rs887797*A / A (p=0.033; OR, 2.03; 95% CI: 1.01-4.11) genotypes, as well as combinations of AGTR1 rs5186*C / C + PRKCA rs1010544*A (p=0.0064; OR, 3.27; 95% CI: 1.32-8.07), AGTR1 rs5186*A + PRKCA rs887797*G (p=0.0021; OR, 0.42; 95 % CI: 0.24-0.75) and AGTR1 rs5186*A / A + CDC42 rs12038474*A (p=0.005; OR, 0.47; 95 % CI: 0.27-0.82). In women, only combinations of PRKCA rs1010544*A + IL10 rs1800896*A / A (p=0.032; OR, 1.94; 95% CI: 1.01-3.74) and PRKCA rs1010544*G + IFNG rs2430561*T / T (p=0.026; OR, 0.20; 95% CI: 0.044-0.96) were associated with the age at first MI.

Conclusion      A number of polymorphic variants of the genome associated with the age at first MI was identified. For the first time, it was shown that the set of such variants differs in men and women.

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