Association study between rs2275913 genetic polymorphism and serum levels of IL-17A with risk of coronary artery disease

Document Type : Original article


1 Cellular and Molecular Research Centre, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

2 Department of Medical Laboratory Sciences, School of Paramedical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran


Coronary artery disease (CAD) is now considered as a main cause of disability and mortality in Iranian population. Inflammatory processes are the initial events in the development of CAD. Interleukin-17A (IL-17A) is a pro-inflammatory cytokine and its genetic variation may contribute to the development of CAD. This study investigated serum levels and the G-197A polymorphism of IL17A in a group of patients with CAD and healthy controls. The study population included 220 angiographically verified CAD patients and 220 healthy controls. Genotyping of G-197A polymorphism of IL17A was done by PCR-RFLP method and serum level of IL-17 was measured by enzyme immunoassay. Results indicated that serum concentration of IL-17A was significantly higher in CAD group than control group (P<0.001). Also, serum levels of IL-17A was significantly higher in carriers of GA and AA genotype relative to carriers of GG genotype in both study population (P<0.05). The G-197A polymorphism of IL17A increased the risk of CAD in mutant homozygous (P=0.007) but not heterozygous (P=0.104) genotype. Moreover, this polymorphism was associated with higher risk of CAD development in allelic (P=0.041) model. However, no significant association was observed between genotypic distribution of G-197A polymorphism and the number of stenotic vessels (P>0.05). In conclusion, the present study indicated G-197A polymorphism of IL17A as a significant contributor to the development but not to the severity of CAD. Moreover, elevated serum levels of IL-17A were identified as a susceptibility marker of CAD.


1. Korosoglou G, Lehrke S, Mueller D, Hosch W, Kauczor HU, Humpert PM, Giannitsis E, Katus HA. Determinants of troponin release in patients with stable coronary artery disease: insights from CT angiography characteristics of atherosclerotic plaque. Heart 2011;97:823-831.
2. Abi Khalil C. The emerging role of epigenetics in cardiovascular disease. Ther Adv Chronic Dis 2014;5:178-187.
3. Dai X, Wiernek S, Evans JP, Runge MS. Genetics of coronary artery disease and myocardial infarction. World J Cardiol 2016;8:1-23. 
4. Galkina E, Ley K. Immune and inflammatory mechanisms of atherosclerosis. Annu Rev Immunol 2009;27:165-197.
5. Ramji DP, Davies TS. Cytokines in atherosclerosis: Key players in all stages of disease and promising therapeutic targets. Cytokine Growth Factor Rev 2015;26:673-685.
6. Seidi A, Mirzaahmadi S, Mahmoodi K, Soleiman-Soltanpour M. The association between NFKB1 -94ATTG ins/del and NFKB1A 826C/T genetic variations and coronary artery disease risk. Mol Biol Res Commun 2018;7:17-24.
7. Gaffen SL. Structure and signalling in the IL-17 receptor family. Nat Rev Immunol 2009;9: 556-567.
8. Cătană CS, Neagoe IB, Cozma V, Magdaş C, Tăbăran F, Dumitraşcu DL. Contribution of the IL-17/IL-23 axis to the pathogenesis of inflammatory bowel disease. World J Gastroenterol 2015;21:5823-5830.
9. Bulat-Kardum LJ, Etokebe GE, Lederer P, Balen S, Dembic Z. Genetic polymorphisms in the toll-like receptor 10, interleukin (IL) 17A and IL17F genes differently affect the risk for tuberculosis in Croatian population. Scand J Immunol 2015;82:63-69. 
10. Hammad A, Mosaad YM, Hammad EM, Elhanbly S, El-Bassiony SR, Al-Harrass MF, Eid R, Sharaf Eldein OA, Alsawah GA, Yahia S, Fawzy IM. Interleukin-17A rs2275913, interleukin-17F rs763780 and rs2397084 gene polymorphisms as possible risk factors in Juvenile lupus and lupus related nephritis. Autoimmunity 2016;49:31-40.
11. Han L, Lee HS, Yoon JH, Choi WS, Park YG, Nam SW, Lee JY, Park WS. Association of IL-17A and IL-17F single nucleotide polymorphisms with susceptibility to osteoarthritis in a Korean population. Gene 2014;533:119-122.
12. Geng GY, Liu HL, Zhao YJ, Wu L, Mao L, Ba N. Correlation between polymorphisms in the IL-17A and IL-17F genes and development of coronary artery disease. Genet Mol Res 2015;14:11488-11494.
13. Zhao Q, Jiang H, Ma T, Qiu H, Guo M, Zhang X. The association between IL-17A and IL-23R polymorphisms and coronary artery disease risk in a Middle Eastern Chinese population. J Clin Lab Anal 2019;33:e22893. 
14. Bao MH, Luo HQ, Xiang J, Tang L, Dong LP, Li GY, Zeng J, Li JM. Meta-analysis for the association between polymorphisms in interleukin-17A and risk of coronary artery disease. Int J Environ Res Public Health 2016;13.
15. Min X, Lu M, Tu S, Wang X, Zhou C, Wang S, Pang S, Qian J, Ge Y, Guo Y, Xu D. Serum cytokine profile in relation to the severity of coronary artery disease. Biomed Res Int 2017; 2017:4013685.
16. Taleb S, Tedgui A, Mallat Z. IL-17 and Th17 cells in atherosclerosis: subtle and contextual roles. Arterioscler Thromb Vasc Biol 2015;35:258-264.  
17. Zheng XS, Wang S, Ni M. Association between interleukin 17A gene polymorphisms and risk of coronary artery disease. Genet Mol Res 2016;15.
18. Miller J, Schwarz W. Aggregate and individual replication probability within an explicit model of the research process. Psychol Methods 2011;16:337-360.
19. Shuang L, Li Z, Chen F, Cui X, Ning Y, Su Y, Dong M. Association between interleukin-17 gene polymorphisms and risk of coronary artery disease. Int J Clin Exp Pathol 2015;8: 11653-11658. 
20. Zacarias JM, Sippert EÂ, Tsuneto PY, Visentainer JE, Sell AM. The influence of interleukin 17A and IL17F polymorphisms on chronic periodontitis disease in Brazilian patients. Mediators Inflamm 2015;2015:147056.
21. Vargas-Alarcón G, Angeles-Martínez J, Villarreal-Molina T, Alvarez-León E, Posadas-Sánchez R, Cardoso-Saldaña G, Ramírez-Bello J, Pérez-Hernández N, Juárez-Rojas JG, Rodríguez-Pérez JM, Fragoso JM. Interleukin-17A gene haplotypes are associated with risk of premature coronary artery disease in Mexican patients from the genetics of atherosclerotic disease (GEA) study. PLoS One 2015;10:e0114943.
22. Espinoza JL, Takami A, Nakata K, Onizuka M, Kawase T, Akiyama H, Miyamura K, Morishima Y, Fukuda T, Kodera Y, Nakao S. A genetic variant in the IL-17 promoter is functionally associated with acute graft-versus-host disease after unrelated bone marrow transplantation. PLoS One 2011;6:e26229.
23.Huang HT, Lu YL, Wang R, Qin HM, Wang CF, Wang JL, Xiang Y, Guo J, Lan Y, Wei YS. The association of IL-17A polymorphisms with IL-17A serum levels and risk of ischemic stroke. Oncotarget 2017;8:103499-103508.