IMPACT OF LOCUS 9P21.3 SINGLE NUCLEOTIDE POLYMORPHISMS ON CORONARY ATHEROSCLEROSIS SEVERITY AND LONG-TERM OUTCOMES AFTER PERCUTANEOUS CORONARY INTERVENTION IN PATIENT WITH MYOCARDIAL INFARCTION

Aim. To investigate association between 9p21.3 locus single nucleotide polymorphisms (SNPs) and coronary atherosclerosis severity and long-term outcomes after percutaneous coronary intervention (PCI) in patients with myocardial infarction (MI).
Material and methods. A total of 255 Caucasian patients (211 male, 44 female; aged up to 65 years, on the average 52.56±7.98 years) with MI were recruited into the study from 01.01.2009 to 30.06.2010. All participants were included into the study after written informed consent. Genome DNA was extracted from leukocytes of venous blood by the phenol-chloroform extraction method. Two SNPs rs10757278 and rs1333049 (locus 9p21.3) were tested by real-time polymerase chain reaction (PCR) according to protocol (probes TaqMan, Applied Biosystems, 7900HT). The coronary angiograms were reviewed by independent angiographers who were blinded to the results of the genotyp- ing (Philips Allura Xper FD10). The total number of lesions, Gensini score and SYNTAX score were derived. Follow-up lasted two years.
Results. Locus 9р21.3 genotypes CC rs1333049 and GG rs10757278 demonstrated a direct strong association with severity of coronary atheromatous burden (left main coro- nary artery stenosis, total number of lesions, Gensini score). There are not influence of locus 9p21.3 on mortality, recurrent MI, hospitalization due to unstable angina, repeated PCI, stroke during follow-up period (6, 12, 24 months). Frequency of the genotype СС rs1333049 among patients with recurrent MI was 20% (without recurrent MI — 27.4%; р=0.54); with hospitalization due to unstable angina — 27.5% (without hospitalization — 26.4%; р=0.82); with repeated PCI — 24.0% (without repeated PCI — 27.2%; р=0.97); among died patients — 29.8% (among survived ones — 26.4%; р=0.76). Frequencies of the genotype GG rs10757278 were similar: recurrent MI (yes — 18.8%; no — 26.4%; р=0.49); hospitalization due to unstable angina (yes — 28%; no — 25.3%; р=0.42); repeated PCI (yes — 23.7%; no — 26.3%; р=0.98); death (yes — 28.6%; no — 25%; р=0.51). Conclusion. Locus 9р21.3 genotypes CC rs1333049 and GG rs10757278 revealed significant association with severity of coronary atheromatous burden in patients with MI. There was no relationship between these genotypes of locus 9р21.3 SNPs and long-term PCI outcomes.

1. Maksimov V.N., Kulikov I.V., Orlov P.S. et al. Evaluation of association between 9 genetic polymorphisms and myocardial infarction in the Siberian population. Vestnik Rossiĭskoĭ Akademii Meditsinskikh Nauk 2012;(5):24–9. Russian (Максимов В.Н., Куликов И.В., Орлов П.С. и др. Проверка взаимосвязи между девятью однонуклеотидными полиморфизмами и инфарктом миокарда на сибирской популяции. Вестник РАМН 2012; (5): 24–9).

2. Shesternya P.A., Shulman V.A., Nikulina S.Yu. Predictive role of chromosome 9p21.3 polymorphisms and their association with family history of coronary heart disease in patients with myocardial infarction. Russian Journal of Cardiology 2012; 6(98): 14–8. Russian (Шестерня П.А., Шульман В.А., Никулина С.Ю. и др. Предикторная роль полиморфизмов хромосомы 9р21.3 и их взаимосвязь с отягощенной наследственностью в развитии инфаркта миокарда. Российский Кардиологический Журнал 2012; 6(98): 14–8).

3. Deloukas P., Kanoni S., Willenborg C. et al. Large-scale association analysis identifies new risk loci for coronary artery disease. Nature Genetics 2012; 45 (1): 25–33.

4. Prins B.P., Lagou V., Asselbergs F.W. et al. Genetics of coronary artery disease: genome-wide association studies and beyond. Atherosclerosis 2012; 225 (1): 1–10.

5. Schunkert H., Erdmann J., Samani N.J. Genetics of myocardial infarction: a progress report. Eur Hear J 2010; 31(8): 918–25.

6. Buysschaert I., Carruthers K.F., Dunbar D.R. et al. A variant at chromosome 9p21 is associated with recurrent myocardial infarction and cardiac death after acute coronary syndrome: The GRACE Genetics Study. Eur Heart J 2010; 31: 1132–41.

7. Patel R.S., Su S., Neeland I.J. et al. The chromosome 9p21 risk locus is associated with angiographic and progression of coronary artery disease. Eur Heart J 2010; 31: 3017–23.

8. Dandona S., Stewart A.F.R., Chen L. et al. Gene dosage of the common variant 9p21 predicts severity of coronary artery disease. J Am Coll Cardiol 2010; 56: 479–86.

9. Chan K., Patel R.S., Newcombe P. et al. Association Between the Chromosome 9p21 Locus and Angiographic Coronary Artery Disease Burden. A Collaborative Meta-Analysis. J Am Coll Cardiol 2013; 61(4): 957–70.

10. Chan K., Motterle A., Laxton R.C. et al. Common variant on chromosome 9p21 predict severity of coro- nary artery disease. J Am Coll Cardiol 2011; 57: 1497–8.

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

12. Montorsi P., Ravagnani P.M., Galli S. et al. Association between erectile dysfunction and coronary artery disease. Role of coronary clinical presentation and extent of coronary vessels involvement: the CO- BRA trial. Eur Heart J 2006; 27: 2632–9.

13. Sianos G., Morel M.A., Kappetein A.P. et al. The SYNTAX score: an angiographic tool grading the complexity of coronary artery disease. EuroIntervention 2005; 1: 219–27.

14. Hinohara K., Nakajima T., Takahashi M. et al. Replication of the association between a chromosome 9p21 polymorphism and coronary artery disease in Japanese and Korean populations. J Hum Genet 2008; 53: 357–9.

15. Shen G.Q., Li L., Rao S. et al. Four SNPs on chromosome 9p21 in a South Korean population implicate a genetic locus that confers high cross-race risk for development of coronary artery disease. Arterioscler Thromb Vasc Biol 2008; 28: 360–5.