SYNE1 gene novel variant is associated with myocardial infarction in young people with a family history of premature atherosclerosis.

Aim. The aim of the study was to investigate the role of genetic variants in young patients (aged <50 years) with myocardial infarction (MI) and a family history of premature atherosclerosis. Methods and Results. The studied group consisted of 70 patients aged 26-49 (mean 43.1, SD ±4.3), 17 women and 53 men, with MI and with a family history of premature atherosclerosis, defined as MI or ischaemic stroke in first-degree relatives at age <65 years in women or <55 years in men. The total DNA was extracted from the peripheral blood samples. The targeted enrichment library was prepared and analyzed using the Next-Generation Sequencing method. Statistical analyses were performed using the R software package (http://www.r-project.org/). The results of sequencing were compared to data from the reference control population consisting of 597 people with no history of MI (418 women, 179 men) aged 18-83 (mean 40.5, SD ± 12.4) as a whole and after matching with a studied group by age and gender in a proportion 1:3 (210 people, 51 women, 159 men, aged 18-77, mean 42.1, SD ±10.6) using Propensity Score Matching. Risks associated with detected variants were evaluated using Fisher?s exact test based on the allelic frequencies of variants in both groups. SYNE1 gene variant rs36215567 (NM_182961.4: c.20396+22A>G) occurs with a significantly higher incidence in the studied group when compared to the control population with OR 4.80 95%CI 1.43-14.45 (p=0.005) as well as when compared to the control population matched by age and gender OR 9.31 95%CI 1.64-95.41 (p=0.004). There were no statistically significant differences in the incidence of variants related to familial hypercholesterolemia such as LDLR c.667G>A, PCSK9 c.658-36G>A, and APOB c.12382G>A between both cohorts. Conclusion. A novel variant of the SYNE1 gene is associated with myocardial infarction in young patients with a family history of premature atherosclerosis.