АССОЦИАЦИЯ RS429358 И RS7412 ГЕНА АРОЕ С РИСКОМ РАЗВИТИЯ ИНФАРКТА МИОКАРДА

Abstract

Introduction. Cardiovascular disease (CVD) is the leading cause of death in industrialized countries. The pathology of lipid metabolism, which underlies the atherosclerotic process, is one of the main risk factors for the development of CVD. Genetic markers of predisposition to the development of lipid metabolism disorders can be used for early diagnosis and development of programs for the primary prevention of CVD. Apolipoprotein E is the main apolipoprotein of chylomicrons and is required for the normal catabolism of triglyceride-rich lipoprotein components. The aim of the study was to analyze the association of rs7412 and rs429358 of the APOE gene with the risk of myocardial infarction (MI) in the population of Western Siberia (Russia). Materials and methods: the main group (9360 people, 45-69 years old, mean age 53.8±7) was formed from residents of Novosibirsk, surveyed in 2003-2005. within the framework of the International multicenter project "Risk Factors for Cardiovascular Diseases in Eastern Europe" HAPIEE. The study protocol was approved by the local ethics committee of NIITPM, a branch of the ICG SB RAS. Informed consent was obtained from each study participant for the examination (including the collection of biological materials). For genetic research, 2690 people were selected from the main group by random number method. After excluding unconfirmed MI cases and non-MI deaths, the sample size was 2286 people. The endpoints of the study were MI, stroke, and death from all causes. Data were obtained from the following sources: (i) clinical re-survey of the sample in 2006-2008, 2015; (II) databases: Novosibirsk City Myocardial Infarction Registry, Novosibirsk City Stroke Registry, and Novosibirsk City Mortality Registry (register data are collected at NIITPM, a branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences from 1988 to the present). The group with MI consisted of 183 people (128 men, 55 women), inclusion criteria: MI that occurred during the observation period (according to all registries and repeated screenings); MI in history, confirmed by instrumental methods of examination. Exclusion criteria: history of MI, not confirmed by instrumental methods of examination. DNA from blood was isolated by phenol-chloroform extraction. Genotyping of rs429358 and rs7412 of the APOE gene was carried out by the Real-Time PCR method on the StepOnePlus Real-Time PCR System (Thermo Fisher Scientific, Foster City, California, USA). Significance of differences in allele frequencies and verification of compliance with the Hardy-Weinberg equilibrium were calculated using Pearson's χ2 test. Results: The association of rs429358 and rs7412 of the APOE gene with the development of MI in men (p = 0.009) and in the general group (p = 0.001) was revealed. Carrying the ɛ2ɛ4 genotype is associated with an increased risk of MI in men (OR = 3.931, 95% CI: 1.772-8.720, p < 0.0001) and in the general group (OR = 3.753, 95% CI: 1.976-7.127, p < 0 ,0001). Conclusion: our study confirmed a statistically significant association between the genotypes rs7412 and rs429358 and the development of MI both in men and in the general group of the population of Western Siberia (Russia). Structural changes in DNA can independently affect the risk of myocardial infarction. Individuals with confirmed increased genetic risk may receive additional motivation to lead a healthy lifestyle. Data on genetic risk factors for pathology can be used to optimize the clinical management of patients.