Association of variants of the APOE, CETP, TRIB1 genes and chromosomal region 9p21.3 with blood lipid parameters and prognosis of myocardial infarction

Cardiovascular diseases, including atherosclerotic diseases, are among the leading causes of morbidity and mortality in Russia. Hyperlipidemia is one of the most common metabolic disorders, leading to the development of atherosclerosis if undiagnosed and untreated. Atherosclerosis is the most common cause of coronary heart disease (CHD), the most unfavorable outcome of which is myocardial infarction (MI). Lipid metabolism disorders can be associated not only with lifestyle but also with genetic predisposition. The aim of this study was to investigate the association of variants in the APOE, CETP, TRIB1 genes, and chromosomal region 9p21.3 with lipid parameters and the prognosis of MI in the Caucasian population of Western Siberia (Russia). Material and methods. The study included 3125 participants of the HAPIEE project (58.3 ± 7 years; men 47.9 %, women 52.1 %). Data on new cases of MI in the observed cohort were collected from the Novosibirsk City Registry of Myocardial Infarction and Mortality Register over 12 years (2003–2015). Genotyping was performed using allele-specific Real-Time PCR with TaqMan technology (Biolabmix, Novosibirsk, Russia) on a CFX-96 Real-Time PCR System (Bio-Rad Laboratories, Inc, USA). Results. Variants rs429358 and rs7412 of the APOE gene were statistically significantly associated with the average levels of TC (p < 0.0001), HDL-C (p = 0.019 in the overall group), LDL-C (p < 0.0001), non-HDL-C, TG (p < 0.0001), and IA (p < 0.0001). A statistically significant association was found between the rs708272 variant of the CETP gene with the level of HDL-C (p < 0.0001), AI (p = 0.001) and the rs1333049 variant of the 9p21.3 region with the level of TC (p = 0.004), LDL-C (p = 0.001), non-HDL-C (p = 0.005) in the group of men. Among the carriers of the rs429358 and rs7412 APOE gene variants, statistically significant differences were found in the prognosis of MI in the group of women (p = 0.0010). For rs708272 of the CETP gene, a statistically significant association was found in the subgroup of men (p = 0.028). For rs1333049 of the 9p21.3 region, statistically significant differences were shown in the overall group (p = 0.010). Conclusion. In this study, a statistically significant association of variants of the APOE, CETP genes and the chromosomal region 9p21.3 with blood lipid parameters, as well as with the prognosis for MI in the group of Caucasian in- habitants of Western Siberia, was revealed.

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