Clinical application of chromosome 9p21.3 genotyping in patients with coronary artery disease

Nikulina,Svetlana; Artyukhov,Ivan; Shesternya,Pavel; Gavrilyuk,Oksana; Maksimov,Vladimir; Voyevoda,Mikhail; Brusentsov,Denis

doi:10.3892/etm.2019.7884

Clinical application of chromosome 9p21.3 genotyping in patients with coronary artery disease

Authors:
- Svetlana Nikulina
- Ivan Artyukhov
- Pavel Shesternya
- Oksana Gavrilyuk
- Vladimir Maksimov
- Mikhail Voyevoda
- Denis Brusentsov
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Affiliations: Department of Internal Diseases No. 1, Professor V.F. Voino‑Yasenetsky Krasnoyarsk State Medical University of The Ministry of Healthcare of The Russian Federation, Krasnoyarsk 660022, Russian Federation, Laboratory of Molecular Genetic Studies of Therapeutic Diseases, Institute of Internal and Preventive Medicine of The Siberian Branch of The Russian Academy of Medical Sciences, Novosibirsk 630089, Russian Federation
Published online on: August 13, 2019 https://doi.org/10.3892/etm.2019.7884
Pages: 3100-3108

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Abstract

The aim of the present study was to investigate the susceptibility of two coronary artery disease (CAD)‑associated single nucleotide polymorphisms on 9p21 (rs1333049 and rs10757278) to myocardial infarction (MI) in a primary (stratification of high risk group for MI) and secondary prevention setting. The prospective observational study included 500 patients with MI [411 males (82.2%) and 89 females (17.8%)] under 65 years. The risk of MI for carriers of the homozygous CC genotype of rs1333049 and homozygous GG genotype of rs10757278 was 1.77 [95% confidence interval (CI): 1.36‑2.37], and 1.70 (95% CI: 1.24‑2.32) respectively. The risk of MI for heterozygous allele carriers was slightly lower. Specifically, the risk of MI was 1.58 (95% CI: 1.18‑2.11) for both heterozygous and homozygous carriers of the rs1333049 C allele, and 1.36 (95% CI: 1.01‑1.83) for the carriers of the rs10757278 G allele. A logistic regression model including sex, age, presence of excess weight or obesity, abdominal obesity, diabetes mellitus, arterial hypertension, hypercholesterolemia, positive family history and smoking status parameters revealed that rs1333049 CC genotype was an independent predictive factor of myocardial infraction [OR=1.71 (95% CI: 1.16‑2.52), P=0.006]. Patients who underwent percutaneous coronary intervention (PCI) during index hospitalization and patients who did not receive PCI were followed up for two years after discharge. Compared with patients with MI who underwent PCI, the risk of recurrent acute coronary syndrome (re‑ACS) was higher among rs1333049 C allele carriers who did not receive PCI during index hospitalization. One year after MI, the OR of re‑ACS was 4.91 (95% CI: 1.45‑16.66), while two years after MI, OR was 3.77 (95% CI: 1.50‑9.52) in those patients who did not receive PCI during index hospitalization. There was no statistically significant association between polymorphic variants of rs1333049 and MI follow‑up outcomes in patients who underwent PCI. The present study indicated clinical utility of 9p21.3 genotyping to predict the outcomes for patients with MI without PCI. Due to the small sample size, this association study forms basis for larger, nationwide studies investigating clinical applications of genetic data.

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1	Prins BP, Lagou V, Asselbergs FW, Snieder H and Fu J: Genetics of coronary artery disease: Genome-wide association studies and beyond. Atherosclerosis. 225:1–10. 2012. View Article : Google Scholar : PubMed/NCBI
2	CARDIoGRAMplusC4D Consortium, ; Deloukas P, Kanoni S, Willenborg C, Farrall M, Assimes TL, Thompson JR, Ingelsson E, Saleheen D, Erdmann J, et al: Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet. 45:25–33. 2013. View Article : Google Scholar : PubMed/NCBI
3	Chan K, Patel RS, Newcombe P, Nelson CP, Qasim A, Epstein SE, Burnett S, Vaccarino VL, Zafari AM, Shah SH, et al: Association between the chromosome 9p21 locus and angiographic coronary artery disease burden: A collaborative meta-analysis. J Am Coll Cardiol. 61:957–970. 2013. View Article : Google Scholar : PubMed/NCBI
4	Franceschini N, Carty C, Bůžková P, Reiner A, Garrett T, Lin Y, Vöckler JS, Hindorff LA, Cole SA, Boerwinkle E, et al: Association of genetic variants and incident coronary heart disease in multi-ethnic cohorts. The PAGE study. Circ Cardiovasc Genet. 4:661–672. 2011. View Article : Google Scholar : PubMed/NCBI
5	Guo J, Li W, Wu Z, Cheng X, Wang Y and Chen T: Association between 9p21.3 genomic markers and coronary artery disease in East Asians: A meta-analysis involving 9813 cases and 10710 controls. Mol Biol Rep. 40:337–343. 2013. View Article : Google Scholar : PubMed/NCBI
6	Horne BD: Chromosome 9p21, risk associations, and biological mechanisms in coronary heart disease. J Am Coll Cardiol. 63:2246–2248. 2014. View Article : Google Scholar : PubMed/NCBI
7	Munir MS, Wang Z, Alahdab F, Steffen MW, Erwin PJ, Kullo IJ and Murad MH: The association of 9p21-3 locus with coronary atherosclerosis: A systematic review and meta-analysis. BMC Med Genet. 6:662014. View Article : Google Scholar
8	Shesternya PA, Shulman VA, Nikulina SYU, Martynova EA, Dyomkina AI, Orlov PS, Maksimov VN and Voyevoda MI: Predictive role of chromosome 9p21.3 polymorphisms and their association with family history of coronary heart disease in patients with myocardial infarction. Russian J Cardiol. 6:14–18. 2012.(In Russian).
9	Tajbakhsh A, Khorrami MS, Hassanian SM, Aghasizade M, Pasdar A, Maftouh M, Tabatabai E, Parizadeh SM, Fazeli M, Ferns GA, et al: The 9p21 locus and its potential role in atherosclerosis susceptibility; Molecular mechanisms and clinical implications. Curr Pharm Des. 22:5730–5737. 2016. View Article : Google Scholar : PubMed/NCBI
10	Ganna A, Magnusson PK, Pedersen NL, de Faire U, Reilly M, Arnöv J, Sundström J, Hamsten A and Ingelsson E: Multilocus genetic risk scores for coronary heart disease prediction. Arterioscler Thromb Vasc Biol. 33:2267–2272. 2013. View Article : Google Scholar : PubMed/NCBI
11	Paynter NP, Chasman DI, Buring JE, Shiffman D, Cook NR and Ridker PM: Cardiovascular disease risk prediction with or without knowledge of genetic variation at chromosome 9p21.3. Ann Intern Med. 150:65–72. 2009. View Article : Google Scholar : PubMed/NCBI
12	Ripatti S, Tikkanen E, Orho-Melander M, Havulinna AS, Silander K, Sharma A, Guiducci C, Perola M, Jula A, Sinisalo J, et al: A multilocus genetic risk score for coronary heart disease: Case-control and prospective cohort analyses. Lancet. 376:1393–1400. 2010. View Article : Google Scholar : PubMed/NCBI
13	Buysschaert I, Carruthers KF, Dunbar DR, Peuteman G, Rietzschel E, Belmans A, Hedley A, De Meyer T, Budaj A, Van de Werf F, 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. 31:1132–1141. 2010. View Article : Google Scholar : PubMed/NCBI
14	Adrissino D, Berzuini C, Merlini PA, Mannuccio Mannucci P, Surti A, Burtt N, Voight B, Tubaro M, Peyvandi F, Spreafico M, et al: Influence of 9p21.3 genetic variants on clinical and angiographic outcomes in early-onset myocardial infarction. J Am Coll Cardiol. 58:426–434. 2011. View Article : Google Scholar : PubMed/NCBI
15	Hoppmann P, Erl A, Türk S, Tiroch K, Mehilli J, Schömig A, Kastrati A and Koch W: No association of chromosome 9p21.3 variation with clinical and angiographic outcomes after placement of drug-eluting stents. JACC Cardiovasc Interv. 2:1149–1155. 2009. View Article : Google Scholar : PubMed/NCBI
16	Szpakowicz A, Kiliszek M, Pepinski W, Waszkiewicz E, Franaszczyk M, Skawronska M, Ploski R, Niemcunowicz- Janica A, Dobrzycki S, Opolski G, et al: Polymorphism of 9p21.3 locus is associated with 5-year survival in high-risk patients with myocardial infarction. PLoS One. 9:e1046352014. View Article : Google Scholar : PubMed/NCBI
17	MONICA Monograph and Multimedia Sourcebook, . World's largest study of heart disease, stroke, risk factors, and population trends 1979–2002. Edited by Hugh Tunstall-Pedoe (with 64 other contributors for the WHO MONICA Project). WHO; Geneva: 2003
18	Malyutina S, Bobak M, Simonova G, Gafarov V, Nikitin Y and Marmot M: Education, marital status, and total and cardiovascular mortality in Novosibirsk, Russia: A prospective cohort study. Ann Epidemiol. 14:244–249. 2004. View Article : Google Scholar : PubMed/NCBI
19	GRACE Investigators, . Rationale and design of the GRACE (Global Registry of Acute Coronary Events) project: A multinational registry of patients hospitalized with acute coronary syndromes. Am Heart J. 141:190–199. 2001. View Article : Google Scholar : PubMed/NCBI
20	Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G, Mautner B, Corbalan R, Radley D and Braunwald E: The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. JAMA. 284:835–842. 2000. View Article : Google Scholar : PubMed/NCBI
21	Patel RS and Ye S: Genetic determinants of coronary heart disease: New discoveries and insights from genome-wide association study. Heart. 97:1463–1473. 2011. View Article : Google Scholar : PubMed/NCBI
22	Gioli-Pereira L, Santos PC, Ferreira NE, Hueb WA, Krieger JE and Pereira AC: Higher incidence of death in multi-vessel coronary artery disease patients associated with polymorphisms in chromosome 9p21. BMC Cardiovasc Disord. 12:612012. View Article : Google Scholar : PubMed/NCBI
23	Hara M, Sakata Y, Nakatani D, Suna S, Usami M, Matsumoto S, Ozaki K, Nishino M, Sato H, Kitamura T, et al: Reduced risk of recurrent myocardial infarction in homozygous carriers of the chromosome 9p21 rs1333049 C risk allele in the contemporary percutaneous coronary intervention era: A prospective observational study. BMJ Open. 4:e0054382014. View Article : Google Scholar : PubMed/NCBI