SYNE1 gene novel variant is associated with myocardial infarction in young people with a family history of premature atherosclerosis
Authors: Ambroziak M , Franke J , Wojcicka A , Kolanowska M , Budaj A 
Published: November 2023

Abstract

Introduction
Genetic background is thought to be responsible for a family occurred premature atherosclerosis, including myocardial infarction (MI).

Purpose
The aim of the study was to investigate the role of genetic variants in young patients (aged &lt;50 years) with MI and family history of premature atherosclerosis.

Methods
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 family history of premature atherosclerosis, defined as MI or ischaemic stroke in first-degree relatives at age &lt;65 years in women or &lt;55 years in men. The mean BMI in the studied group was 28.8 kg/m2 (SD ±3.5), total cholesterol level 202.3 mg/dl (SD ±3.5), HDL 40.6 mg/dl (SD ±9.6), LDL 124.0 mg/dl (SD ±28.9), triglycerides 164.4 mg/dl (SD ±63.5), glucose 108.3 mg/dl (SD ±19.9) and creatinine 0.9 mg/dl (SD ±0.2). Regarding other risk factors 63 patients (90%) were smokers (mean 24.1 pack-years, SD ±13.0), 44 (62.8%) had hypertension, 11 (15.7%) had diabetes mellitus, and 8 (11.4%) had depression. All patients had diagnosed MI including MI with ST elevation (STEMI) in 18 cases (25.7%) and MI without ST elevation (NSTEMI) in 52 cases (74.3%). All patients, except 2 (no consent), had performed coronary angiography revealing 1-vessel coronary artery disease (VCAD) in 33 patients (47.1%), 2-VCAD in 17 patients (24.3%), and 3-VCAD in 20 patients (28.6%). The mean left ventricular ejection fraction (LVEF) was 51.8% (SD ±8.0).
The total DNA has been extracted from whole peripheral blood samples. The targeted enrichment library was prepared and analyzed using New Generation Sequencing method on Hiseq4000, 2x150 cycles. Statistical analyses were performed using the R software package (www.r-project.org/). The results of sequencing were compared to data from the reference control population consisting of 597 healthy people (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 and 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.

Results
SYNE1 gene variant rs36215567 (NM_182961.4: c.20396+22A&gt;G) has been detected in statistically significant higher incidence in the studied group in comparison to the control population (p=0.005) with OR=4,80 (95%CI 1,43-14,45) as well as when compared to the control population matched by age and gender (p=0.004) OR=9,31 (95%CI 1,64-95,41). There were no statistically significant differences in the incidence of familial hypercholesterolemia related gene variants: LDLR c.667G&gt;A, PCSK9 c.658-36G&gt;A, PCSK9 c.996+55C&gt;A and APOB c.12382G&gt;A between both cohorts.

Conclusion
A novel variant of SYNE1 gene is associated with myocardial infarction in young age patients with a family history of premature atherosclerosis.