Abstract

Aim. To evaluate the utilization of complex significance evaluation in Russian population, of genetic markers of myocardial infarction identified in entire-genomic associative studies. Material and methods . Group of MI patients (n=200) and control group (n=420) were created based on populational selection of 45-69 year old citizens of Novosibirsk (9400 persons), collected during the international project HAPIEE; myocardial infarction patients, admitted to intensive care unit of the Hospital № 1 (160 persons); sudden cardiac death victims, post forensic investigation (n=285). Longevity group was collected during home visits and in the nursing houses (n=85). Genomic DNA was extracted from venous blood and myocardial tissue by phenolchlorophorm method. Genes polymorphism was tested with PCR real-time according to the protocol by equipment developer (TaqMan, Applied Biosystems, USA), device ABI 7900HT. For the study, the following MNP were selected: rs499818, rs619203, rs10757278 and rs1333049 (chr. 9), rs1376251, rs2549513, rs4804611, rs17465637. Results. Mononucleotide polymorphisms, that did not show differences at pretest stage, showed significant distinctions in the studied population. Two MNP were closely linked: rs10757278 and rs1333049 (chr. 9) so for further assessment the rs1333049 was retained. Among other seven, only five MNP showed relation with MI of various strength. Some, like the rs1333049 showed association with MI in all groups and subgroups, while the others — only in separate groups, with restriction by sex and gender. The rs2549513 and rs17465637 showed to be not associated with CHD at all, though rs2549513 showed association with lipid and glucose metabolism, as with the severity of coronary atherosclerosis and adverse prognosis for 1 year post-MI. The rs17465637 was just poorly associated with BMI. Conclusion. Complex approach to assessment of polymorphism role is quite demanding, but provides with a high grade of insurance in the significance of the results obtained, of non-random character of the results, and makes it to choose the most credible, that have showed association not only with the main pathological phenotype, but with its risk factors.

Highlights

  • В группе с благоприятным прогнозом достоверно чаще встречался генотип АА (70,6% vs 53%), отношение шансов (ОШ) =0,47 (95% ДИ 0,26-0,85)

  • Buysschaert I, Carruthers KF, Dunbar DR, et al A variant at chromosome 9p21 is associated with recurrent myocardial infarction and cardiac death after acute coronary syndrome: The GRACE Genetics Study

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Summary

ОРИГИНАЛЬНЫЕ СТАТЬИ

КОМПЛЕКСНЫЙ ПОДХОД ПРИ ОЦЕНКЕ ИНФОРМАТИВНОСТИ В РОССИЙСКОЙ ПОПУЛЯЦИИ ГЕНЕТИЧЕСКИХ МАРКЕРОВ, АССОЦИИРОВАННЫХ С ИНФАРКТОМ МИОКАРДА И ЕГО ФАКТОРАМИ РИСКА. Лабораторией молекулярно-генетических исследований терапевтических заболеваний, Орлов П. С. лаборатории молекулярно-генетических исследований терапевтических заболеваний, Иванова А. Лаборатории молекулярно-генетических исследований терапевтических заболеваний, Ложкина Н. М.н., доцент кафедры факультетской терапии лечебного факультета, Куимов А. ВОЗ — Всемирная Организация Здравоохранения, ВСС — внезапная сердечная смерть, ИБС — ишемическая болезнь сердца, ИМ — инфаркт миокарда, ИМТ — индекс массы тела, КА — коронарный атеросклероз, ЛПВП — липопротеины высокой плотности, ЛПНП — липопротеины низкой плотности, ОКС — острый коронарный синдром, ОНП — однонуклеотидный полиморфизм, ОХС — общий холестерин, ОШ — отношение шансов, ССЗ — сердечно-сосудистые заболевания, ФВЛЖ — фракция выброса левого желудочка, ЧСС — частота сердечных сокращений, HAPIEE — Health, Alcohol and Psychosocial factors In Eastern Europe.

Conclusion
Findings
Внезапная смерть n

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