Background: Several studies illustrated that IL-23/Th17 axis could be an important pro-inflammatory pathway in atherosclerosis. As a key element in this inflammatory mechanism, interleukin-23 receptor (IL-23R) may play a critical role in the pathological process of atherosclerosis. Single nucleotide polymorphisms (SNPs) in IL-23R have recently been consistently found to be associated with atherosclerosis diseases. However, its association with acute coronary syndrome (ACS) is still indistinct. Here, we discussed whether genetic polymorphisms in IL-23R (rs11209026 G/A) were associated with susceptibility to ACS. Methods: Among 160 patients with ACS, it includes 80 patients with unstable angina pectoris (UAP), 80 patients with myocardial infarction (MI), and 80 control subjects were selected randomly. The polymorphisms of IL-23R (rs11209026 G/A) were analyzed by the Sanger method. Results: Data showed that percentages of rs11209026 AG genotypes were significantly lower in ACS group (including: UAP and MI) than in controls (odds ratio [OR] = 0.324, 95% confidence interval [CI]: 0.148 - 0.712, p = 0.005; OR = 0.351, 95% CI: 0.135 - 0.910, p = 0.031; OR = 0.303, 95% CI: 0.112 - 0.817, p = 0.018, respectively). Furthermore, there was no correlation between rs11209026 G/A SNP and dyslipidemia-associated ACS. Conclusions: The variant of the rs11209026 polymorphism in IL-23R gene might decrease the risk of ACS, and these data suggest that AG genotype of the rs11209026 G/A polymorphism may act as a protective factor for acute coronary syndrome and subtype of ACS.
References
[1]
Mozaffarian, D., Benjamin, E.J., et al. (2016) Executive Summary: Heart Disease and Stroke Statistics—2016 Update: A Report from the American Heart Association. Circulation, 133, 447-454. https://doi.org/10.1161/CIR.0000000000000366
[2]
Tabas, I. and Lichtman, A.H. (2017) Monocyte-Macrophages and T Cells in Atherosclerosis. Immunity, 47, 621-634. https://doi.org/10.1016/j.immuni.2017.09.008
[3]
Crea, F. and Liuzzo, G. (2013) Pathogenesis of Acute Coronary Syndromes. Journal of the American College of Cardiology, 61, 1-11. https://doi.org/10.1016/j.jacc.2012.07.064
[4]
Su, S.A., Ma, H., Shen, L., et al. (2013) Interleukin-17 and Acute Coronary Syndrome. Journal of Zhejiang University Science B, 14, 664-669. https://doi.org/10.1631/jzus.BQICC701
[5]
Behzadi, P., Behzadi, E. and Ranjbar, R. (2016) IL-12 Family Cytokines: General Characteristics, Pathogenic Microorganisms, Receptors, and Signalling Pathways. Acta Microbiologica et Immunologica Hungarica, 63, 1-25. https://doi.org/10.1556/030.63.2016.1.1
[6]
Fragoulis, G.E., Siebert, S. and McInnes, I.B. (2016) Therapeutic Targeting of IL-17 and IL-23 Cytokines in Immune-Mediated Diseases. Annual Review of Medicine, 67, 337-353.
[7]
Gaffen, S.L., Jain, R., Garg, A.V., et al. (2014) The IL-23-IL-17 Immune Axis: From Mechanisms to Therapeutic Testing. Nature Reviews Immunology, 14, 585-600. https://doi.org/10.1038/nri3707
[8]
Abbas, A., Gregersen, I., Holm, S., et al. (2015) Interleukin 23 Levels Are Increased in Carotid Atherosclerosis: Possible Role for the Interleukin 23/Interleukin 17 Axis. Stroke, 46, 793-799. https://doi.org/10.1161/STROKEAHA.114.006516
[9]
Zhang, M., Cai, Z.R., Zhang, B., et al. (2014) Functional Polymorphisms in Interleukin-23 Receptor and Susceptibility to Coronary Artery Disease. DNA and Cell Biology, 33, 891-897. https://doi.org/10.1089/dna.2014.2573
[10]
Kave, M., Shadman, M., Alizadeh, A., et al. (2015) Analysis of the Association between IL-23R rs11209026 Polymorphism and Incidence of Atherosclerosis. International Journal of Immunogenetics, 42, 341-345. https://doi.org/10.1111/iji.12223
[11]
Erbel, C., Dengler, T.J., Wangler, S., et al. (2011) Expression of IL-17A in Human Atherosclerotic Lesions Is Associated with Increased Inflammation and Plaque Vulnerability. Basic Research in Cardiology, 106, 125-134. https://doi.org/10.1007/s00395-010-0135-y
[12]
Fischer, K., Przepiera-Bedzak, H., Sawicki, M., et al. (2017) Serum Interleukin-23 in Polish Patients with Systemic Lupus Erythematosus: Association with Lupus Nephritis, Obesity, and Peripheral Vascular Disease. Mediators of Inflammation, 2017, Article ID: 9401432.
[13]
Ma, S., Zhong, D., Chen, H., et al. (2013) The Immunomodulatory Effect of Bone Marrow Stromal Cells (BMSCs) on Interleukin (IL)-23/IL-17-Mediated Ischemic Stroke in Mice. Journal of Neuroimmunology, 257, 28-35. https://doi.org/10.1016/j.jneuroim.2013.01.007
[14]
Mangino, M., Braund, P., Singh, R., et al. (2008) Association Analysis of IL-12B and IL-23R Polymorphisms in Myocardial Infarction. Journal of Molecular Medicine, 86, 99-103. https://doi.org/10.1007/s00109-007-0264-4
[15]
Raad, M.A., Chams, N.H. and Sharara, A.I. (2016) New and Evolving Immunotherapy in Inflammatory Bowel Disease. Inflammatory Intestinal Diseases, 1, 85-95. https://doi.org/10.1159/000445986
[16]
Can, G., Tezel, A., Gurkan, H., et al. (2016) Investigation of IL23R, JAK2, and STAT3 Gene Polymorphisms and Gene-Gene Interactions in Crohn’s Disease and Ulcerative Colitis in a Turkish Population. The Turkish Journal of Gastroenterology: The Official Journal of Turkish Society of Gastroenterology, 27, 525-536. https://doi.org/10.5152/tjg.2016.16327
[17]
Yu, R.Y., Brazaitis, J. and Gallagher, G. (2015) The Human IL-23 Receptor rs11209026 A Allele Promotes the Expression of a Soluble IL-23R-Encoding mRNA Species. Journal of Immunology, 194, 1062-1068. https://doi.org/10.4049/jimmunol.1401850
[18]
Abdollahi, E., Tavasolian, F., Momtazi-Borojeni, A.A., et al. (2016) Protective Role of R381Q (rs11209026) Polymorphism in IL-23R Gene in Immune-Mediated Diseases: A Comprehensive Review. Journal of Immunotoxicology, 13, 286-300. https://doi.org/10.3109/1547691X.2015.1115448
[19]
Di Meglio, P., Di Cesare, A., Laggner, U., et al. (2011) The IL23R R381Q Gene Variant Protects against Immune-Mediated Diseases by Impairing IL-23-Induced Th17 Effector Response in Humans. PloS ONE, 6, e17160. https://doi.org/10.1371/journal.pone.0017160
[20]
Pidasheva, S., Trifari, S., Phillips, A., et al. (2011) Functional Studies on the IBD Susceptibility Gene IL23R Implicate Reduced Receptor Function in the Protective Genetic Variant R381Q. PloS ONE, 6, e25038. https://doi.org/10.1371/journal.pone.0025038