Single nucleotide polymorphisms rs1008832 of the CACNA1C gene, rs4027402 of the SYNE2 gene, rs2340917 of the TMEM43 gene, rs58225473 of the CACNB2 gene were found by sequencing the clinical exome of a group of men who died of sudden cardiac death (SCD) at the age of 45 years. The aim of the study is to study the association of single nucleotide polymorphisms rs1008832 of the CACNA1C gene, rs4027402 of the SYNE2 gene, rs2340917 of the TMEM43 gene, rs58225473 of the CACNB2 gene with SCD in a case-control study using routine molecular genetic analysis. Material and methods. SCD group (n = 400, mean age 53.2 ± 8.7 years, 70.9 % men, 29.1 % women) was formed using the SCD criteria of the European Society of Cardiology from the anonymous DNA bank of the deceased sudden death (1999–2019). The control group (n = 400, mean age 53.1 ± 8.3 years, 68.3 % men, 31.7 % women) was matched by sex and age to the SCD group from DNA banks of international projects MONICA and HAPIEE of living at the time of researches participants. Genotyping was carried out using the polymerase chain reaction followed by analysis of restriction fragment length polymorphism. Results. There were no statistically significant differences in the frequencies of genotypes and alleles of single nucleotide polymorphisms rs1008832 of the CACNA1C gene, rs4027402 of the SYNE2 gene, rs2340917 of the TMEM43 gene, rs58225473 of the CACNB2 gene between the SCD group and the control group (p > 0.05). Conclusions. The association of single nucleotide rs1008832 of the CACNA1C gene, rs4027402 of the SYNE2 gene, rs2340917 of the TMEM43 gene, rs58225473 of the CACNB2 gene with SCD has not been confirmed.

Исследована ассоциация между относительной длиной теломер лейкоцитов (ДТЛ), количеством копий митохондриальной ДНК (ККмтДНК) лейкоцитов и развитием острого коронарного синдрома в 15-летнем наблюдении. Случайная популяционная выборка была исходно обследована в 2003-2005 гг. ( n =9 360, мужчины и женщины 45-69 лет, Новосибирск, проект HAPIEE) и наблюдалась в среднем в течение 15 лет. В настоящем анализе были сформированы группы по дизайну гнездовой случай-контроль; случай - новый (Incident) инфаркт миокарда/острый коронарный синдром (ИМ/ОКС) без предшествующей истории сердечно-сосудистых заболеваний (ССЗ) - ИМ, ОКС, инсульт ( n =256), и стратифицированная по полу и возрасту контрольная группа без предшествующей истории ССЗ, рака и без фатальных исходов на период окончания наблюдения ( n =799). С помощью количественной ПЦР в реальном времени был выполнен анализ относительной ДТЛ и ККмтДНК. Носители коротких теломер имели повышенный риск развития ИМ/ОКС в течение последующих 15 лет (ОР=1,87; 95 % ДИ 1,70-2,06) на каждый дециль ДТЛ независимо от других факторов. Меньшее ККмтДНК ассоциировалось с риском развития ИМ/ОКС (ОР=1,19; 95 % ДИ 1,12-1,26) на каждый дециль ККмтДНК независимо от других факторов. Выявленные ассоциации подтверждены в терцильном и пошаговом анализе с непрерывными переменными для обоих биомаркеров. Связи сохранялись после поправки на пол, возраст и традиционные факторы риска ССЗ. ДТЛ и ККмтДНК являются независимыми прогностическими факторами 15-летнего риска развития ИМ/ОКС в сибирской (европеоидной) популяционной когорте среднего и пожилого возраста. Эти данные подчеркивают необходимость дальнейших исследований для выяснения механизмов, через которые ДТЛ и ККмтДНК могут влиять на здоровье человека. We studied the relationship between the leucocyte telomere length (LTL) and the copy number of mitochondrial DNA (CNmtDNA) and the development of acute coronary syndrome during 15 years of follow-up. A random population sample was examined at baseline in 2003-2005 ( n =9 360, men and women 45-69 years old, Novosibirsk, the HAPIEE project) and followed-up for 15 years. In the frame of nested case-control design, we selected cases - incident myocardial infarction/acute coronary syndrome (MI/ACS) among those free from baseline CVD ( n =256) and sex- and age-stratified control among those free from baseline CVD and cancer and alive by the end of follow-up ( n =799). The relative LTL and CNmtDNA were assessed using quantitative real-time PCR. Results. The carriers of shorter telomeres had increased 15-year risk of MI/ACS with adjusted OR=1,87 (95 % CI 1,70-2,06) per 1 LTL decile independent of other factors. Fewer CNmtDNA was associated with increased risk of MI/ACS with adjusted OR=1,19 (95 % CI 1,12-1,26) per 1 CNmtDNA decile. The identified associations were confirmed in tertile analysis and in stepwise analysis with continuous variables of both biomarkers. All associations persisted after adjusting for gender, age, and traditional CVD risk factors. Conclusion. The LTL and CNmtDNA were independent predictors of the 15- year risk of MI/ACS in the middle- and elderly Siberian (Caucasoid) population cohort. These findings highlight the need for further research to elucidate the mechanisms by which LTL and mtDNA copy number may affect human health.

BACKGROUND: The prevalence of Type 2 diabetes mellitus (T2DM) has reached epidemic proportions and it is estimated to affect over 400 million people worldwide. Moreover, the incidence of diabetes is expected to continue to rise and it is projected to affect nearly one of the three individuals by the year 2050. These alarming projections suggest that there is an urgent need for the development and implementation of novel prevention and treatment strategies to combat the rise in T2DM.AIM: To study the possibility of using polymorphisms of genes SLC30A8 and MC4R as markers for predicting the development of T2D in the population of Novosibirsk.MATERIALS AND METHODS: On the basis of prospective follow-up of a representative population sample of residents of Novosibirsk (The HAPIEE Project), 2 groups were formed according to the “case-control” principle (case — people who had diabetes mellitus 2 over 10 years of follow-up, and control — people who did not developed disorders of carbohydrate metabolism). T2D group (n = 443, mean age 56.2 ± 6.7 years, men — 29.6%, women — 70.4%), control group (n = 532, mean age 56.1 ± 7.1 years, men — 32.7%, women — 67.3%). DNA was isolated by phenol-chloroform extraction. Genotyping was performed by the method of polymerase chain reaction with subsequent analysis of restriction fragment length polymorphism, polymerase chain reaction in real time. Statistical processing was carried out using the SPSS 16.0 software package.RESULTS: Genotype TT rs13266634 of the SLC30A8 gene was associated with the risk of developing T2D (relative risk — RR 1.51, 95% confidence interval — CI 1.11–2.05, p =0.008). The CC genotype rs13266634 of the SLC30A8 gene was associated with a protective effect against T2D (RR 0.57, 95% CI 0.35–0.92, p=0.026). No significant effect of rs17782313 of the MC4R gene on the risk of developing T2D was found.CONCLUSION: The rs13266634 polymorphism of the SLC30A8 gene confirmed its association with the prognosis of the development of T2D, which indicates the possibility of considering it as a candidate for inclusion in a diabetes risk score. The association between polymorphisms rs17782313 of the MC4R gene and the prognosis of the development of T2D was not found.