PROSPECTS FOR THE USE OF GENOTYPING FOR CHROMOSOME 9p21.3 POLYMORPHISMS FOR MYOCARDIAL INFARCTION RISK STRATIFICATION IN YOUNG PEOPLE

Objective: to study whether genotyping for single nucleotide polymorphisms (SNPs) rs10757278 and rs1333049 on the 9p21.3 locus may be applied to myocardial infarction (MI) risk stratification using the SCORE scale in young people (less than 45 years).

Subjects and methods. A group of patients with MI (n = 103) and a control group (n = 111) showed no statistically significant differences in
gender, age, hypertension, diabetes mellitus, hypercholesterolemia, overweight and obesity, abdominal obesity, and smoking history. The phenolchloroform method was employed to extract genomic DNA from venous blood. Genetic tests were carried out using real-time polymerase
chain reaction systems (TagMan and AB 7900HT).

Results. There was a statistically significant association of rs1333049 and rs 10757278 with the development of MI. The odds ratio for the latter was 2.53 (95 % confidence interval (CI) 1.31-4.89) in carriers of the risk allele C of rs1333049 and 2.11 (95 % CI 1.11–4.01) in those with the risk allele G of rs10757278. The statistical significance also remained with consideration for the family history of MI. Multiple logistic regression analysis established that the presence of the C allele of rs1333049 in the genotype was of great predictive value as compared with the high/very high risk of fatal and nonfatal events according to the SCORE scale.

Conclusion. SNPs 1333049 and rs10757278 on the 9p21.3 locus are the predictors of MI in young people, which are independent of both traditional risk factors and family history. Having regard to the pattern of an association, it will suffice to genotype one of them, namely rs 1333049, in our population

1. Оганов Р.Г., Концевая А.В., Калинина А.М. Экономический ущерб от сердечно-сосудистых заболеваний в Российской Федерации. Кардиоваскул тер и профил 2011;10(4):4–9.

2. Оганов Р.Г., Масленникова Г.Я. Демографические тенденции в Российской Федерации: вклад болезней системы кровообращения. Кардиоваскул тер и профил 2012;11(1):5–10.

3. Федеральная служба государственной статистики http://www.gks.ru/wps/wcm/connect/rosstat_main/rosstat/ru/statistics/population/demography.

4. Зволинская Е.Ю., Александров А.А. Оценка риска развития сердечно-сосудистых заболеваний у лиц молодого возраста. Кардиология 2010;50(8):37–47.

5. Кардиоваскулярная профилактика. Российские рекомендации ВНОК. Кардиоваскул тер и профил 2011;(6 Прил 2):7–64.

6. Осипов А.Г., Силкина С.Б., Правдина Е.А. и др. Факторы риска и относительный коронарный риск у лиц молодого возраста. Кардиоваскул тер и профил 2012;1(S1):41–2.

7. Гафаров В.В., Громова Е.А., Гафарова А.В. и др. Инфаркт миокарда и стресс на работе и в семье: 10-летний риск возникновения в открытой популяции мужчин 25–64 лет (эпидемиологическое исследование в рамках программы ВОЗ «MONICA-PSYCHOSOCIAL»). Кардиология 2011;51(3):10–6.

8. Голофеевский В.Ю., Сотников А.В., Яковлев В.В., Литвиненко В.А. Особенности течения инфаркта миокарда в молодом и среднем возрасте. Клин мед 2009;87(2):21–4.

9. Сафарова М.С., Ежов М.В., Лупанов В.П. и др. Инфаркт миокарда у молодого мужчины без классических факторов риска атеросклероза. Кардиоваскул тер и профил 2010;9(5):86–90.

10. Schunkert H., König I.R., Kathiresan S. et al. Large-scale association analyses identifies 13 new susceptibility loci for coronary artery disease. Nat Genet 2011;43(4):333–8.

11. Максимов В.Н., Куликов И.В., Орлов П.С. и др. Проверка взаимосвязи между девятью однонуклеотидными полиморфизмами и инфарктом миокарда на сибирской популяции. Вестн РАМН 2012;(5):24–9.

12. Franceschini N., Carty C., Buzkova P. et al. Association of genetic variants and incident coronary heart disease in multiethnic cohorts: the PAGE study. Circ Cardiovasc Genet 2011;4(6):661–72.

13. Hiura Y., Fukushima Y., Yuno M. et al. Validation of the association of genetic variants on chromosome 9p21 and 1q41 with myocardial infarction in a Japanese population. Circ J 2008;72(8):1213–7.

14. Koch W., Türk S., Erl A. et al. The chromosome 9p21 region and myocardial infarction in a European population. Atherosclerosis 2011;217(1):220–6.

15. Maitra A., Dash D., John S. et al. A common variant in chromosome 9p21 associated with coronary artery disease in Asian Indians. J Genet 2010;88(1):113–8.

16. Shen G.Q., Rao S., Martinelli N. et al. Association between four SNP’s on chromosome 9p21 and myocardial infarction is replicated in an Italian population. J Hum Gen 2008;53(2):144–50.

17. Chen Z., Qian Q., Ma G. et al. A common variant on chromosome 9p21 affects the risk of early-onset coronary artery disease. Mol Biol Rep 2009;36(5):889–93.

18. Ellis K.L., Pilbrow A.P., Frampton C.M. et al. A common variant at chromosome 9p21.3 is associated with age of onset of coronary disease but not subsequent mortality. Circ Cardiovasc Genet 2010;3(3):286–93.

19. McPherson R. Chromosome 9p21 and coronary artery disease. N Engl J Med 2010;362(18):1736–7.

20. Scheffold T., Kullmann S., Huge A. et al. Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry. BMC Cardiovasc Disord 2011;(11):9.

21. Adrissino D., Berzuini C., Merlini P.A. et al. Influence of 9p21.3 genetic variants on clinical and angiographic outcomes in earlyonset myocardial infarction. J Am Coll Cardiol 2011;58(4):426–34.

22. Смит К., Калко С., Кантор Ч. Пульсэлектрофорез и методы работы с большими молекулами ДНК. В кн.: Анализ генома. Под ред. К. Дейвиса (пер. с англ.). М.: Мир, 1990. С. 58–94.

23. Virani S.S., Brautbar A., Lee V.V. et al. Chromosome 9p21 single nucleotide polymorphisms are not associated with recurrent myocardial infarction in patients with established coronary artery disease. Circ J 2012;76(4):950–6.