Evaluation of Relationship Between Single-Nucleotide Polymorphism in TNF-Gene Promoter and Susceptibility to Atherosclerosis in Fatemeh Zahra Hospital

Abstract

Introduction: Tumor necrosis factor alpha is a proinflammatory cytokine that initiates a polyvalent initial response of inflammatory cells, which is facilitated by coronary atherosclerosis. Further, it appears that the polymorphism and susceptibility to atherosclerosis are related to the TNF-α gene promoter. Aim: To assay single nucleotide polymorphisms of the TNF-α gene promoter in two sites (863 and 308) in atherosclerotic patients referred to Fatemeh al-Zahra Hospital.
Materials and Methods: This case-control study was conducted on 120 patients (with stenosis greater than 50%) and 120 healthy individuals (with stenosis lesser than 10%). Genomic DNA was extracted using the Phenol-chloroform procedure from their white blood cells. Genotypes of these individuals and TNF-α gene polymorphisms were analyzed by the RFLP-PCR method. Genotype frequencies, the Hardy-Weinberg
equilibrium test, and chi-square analysis were conducted using the SPSS software version 22.
Results: Genotype frequencies of GA, GG, and AA in position -308 of the TNF-α gene of patients were 12.5%, 75%, and 12.5%, respectively; in healthy subjects, they were 7.5%, 21.7%, and 70.8%, respectively. Allele A to G allele increased the risk of disease by 12.716%. The genotype frequencies of AC, CC, and AA in position -863 of the TNFα gene of patients were 3.3%, 69.2%, and 27.5%, respectively; in healthy individuals, they were 2.5%, 11.7%, and 85.8%, respectively. Allele A to C allele increased the risk of disease by 16.373%. Statistical analysis revealed a significant correlation between the risk of atherosclerosis with single nucleotide polymorphisms in the TNF-α gene-863 at C < A and in gene -308 at G < A (P < 0.05).

References
[1] Jones DP, Patel J.Therapeutic Approaches Targeting Inflammation in Cardiovascular Disorders Biology (Basel). 2018 ;16(7):4-8

[2] R., R. Atherosclerosis – An inflammatory disease. N Engl J Med. 1999;340(2): 115–26.

[3] Libby P, R. P., Maseri, A. Inflammation and atherosclerosis. Circulation.2002;105(9):1135–43.

[4] Wang Q, Shang Y, Li S, Wu Y, Wang C, Yan X.Complete heart block in systemic sclerosis: A case report and literature review. Medicine (Baltimore). 2018 ;97(46):e13226.

[5] Skoog T, D.W., Boquist S, Skoglund-Andersson C, Karpe F, Tang R, et al. Plasma tumour necrosis factor-a and early carotid atherosclerosis in healthy middle-aged men. Eur Artery J. 2002;23:376–83.

[6] Bemelmans MH, v.T.L., BuurmanWA. Tumor necrosis factor: Function, release and clearance. Crit Rev Immunol. 1996;16(1):1–11.

[7] Bochner BS, L.F., Gimbrone Jr MA, Newman W, Sterbinsky SA, Derse EA, Anthony CP. Adhesion of human basophils, eosinophils, and neutrophils to interleukin 1- activated human vascular endothelial cells: contributions of endothelial cell adhesion molecules. J Exp Med. 1991;173(6):1553–57.

[8] A., M. The interplay between primary and secondary cytokines. Cytokines involved in the regulation of monocyte recruitment. Drugs. 1997;54(1):15–23.

[9] Feingold KR, G.C. Role of cytokines in inducing hyperlipidemia. Diabetes. 1992;41(2):97–101.

[10] Hotamisligil GS, S.N., Spiegelman BM. Adipose expression of tumor necrosis factoralpha: direct role in obesity-linked insulin resistance. Science. 1993;259(5091):87–91.

[11] Ridker PM, R.N., Pfeffer M, Sacks F, Lepage S, Braunwald E. Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction. Circulation. 2000;101:2149–53.

[12] Valgimigli M, C.C., Malagutti P, Merli E, Soukhomovskaia O, Francolini G, et al., Tumor necrosis factoralpha receptor 1 is a major predictor of mortality and new-onset artery failure in patients with acute myocardial infarction: the cytokine-activation and longterm prognosis in myocardial infarction (C-ALPHA) study. Circulation. 2005;111:863–70.

[13] Cesari M, P.B., Newman AB, Kritchevsky SB, Nicklas BJ, Sutton-Tyrrell K, et al. Inflammatory markers and onset of cardiovascular events: results from the Health ABC Study. Circulation. 2003;108:2317–22.

[14] Cesari M, P.B., Newman AB, Kritchevsky SB, Nicklas BJ, Sutton-Tyrrell K, et al. Inflammatory markers and onset of cardiovascular events: results from the Health ABC study. Circulation. 2003;108(19):2317–22.

[15] Khot UN, K.M., Bajzer CT, Sapp SK, Ohman EM, Brener SJ, et al. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA. 2003;290(7):898–904.

[16] Haddy N, S.C., Droesch S, Zaiou M, Siest G, Ponthieux A, et al. IL-6, TNF-α, and atherosclerosis risk indicators in a healthy family population: the STANISLAS cohort. Atherosclerosis. 2003;170(2):277–83.

[17] [CITATION INCOMPLETE; PLEASE INCLUDE AUTHOR LIST AND FULL TITLE] in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci USA. 1997;94:3195–99.

[18] Pai JK, P.T., Ma J, Manson JE, Hankinson SE, Joshipura K, et al. Inflammatory markers and the risk of coronary heart disease in men and women. N Engl J Med. 2004;351:2599–610.

[19] Vendrell J, F.-R.J., Gutierrez C, Zamora A, Simon I, Bardaji A, et al. A polymorphism in the promoter of the tumor necrosis factor-alpha gene (y308) is associated with coronary heart disease in type 2 diabetic patients. Atherosclerosis. 2003;167:257– 64.

[20] Abraham LJ, K.K. Impact of the -308 TNF promoter polymorphism on the transcriptional regulation of the TNF gene: relevance to disease. J Leukoc Biol. 1999;66(4):562–66.

[21] Kaluza W, R.E., Grossmann S, Hug R, Schopf RE, Galle PR, et al. , Different transcriptional activity and in vitro TNF-α production in psoriasis patients carrying the TNF-α 238A promoter polymorphism. J Invest Dermatol., 2000. 114(6): p. 1180–3.

[23] Kaluza W, R.E., Grossmann S, Hug R, Schopf RE, Galle PR, et al. Different transcriptional activity and in vitro TNF-α production in psoriasis patients carrying the TNF-α 238A promoter polymorphism. J Invest Dermatol. 2000;114(6):1180–83.

[23] Chisari FV, F.C. Hepatitis B virus immunopathogenesis. Annu Rev Immunol.1995;13:29–60.

[24] Gao QJ, L.D., Zhang SY, Jia M, Wang LM, Wu LH, et al. Polymorphisms of some cytokines and chronic hepatitis B and C virus infection. World J Gastroenterol. 2009;15(44):5610–19.

[25] Bayley J, O.T., Verweij C. Is there a future for TNF promoter polymorphisms? Genes Immune J. 2004;5:315–29.

[26] Liping H, J.H., Lu XF, Wang LY, Fan ZJ, Gu DF. Polymorphisms of Tumor necrosis factor alpha gene and coronary heart disease in a Chinese Han population: Interaction with cigarette smoking. Thrombosis Res. 2009;123:822–26.

[27] Koch W, K.A., Bo¨ ttiger C, Mehilli J, von Beckerath N, Scho¨mig A. Interleukin-10 and tumor necrosis factor gene polymorphisms and risk of coronary artery disease and myocardial infarction .Atherosclerosis. 2001;159:137–44.

[28] Yamada Y, I.S., Izawa H, Tanaka M, Yokota M. Genetic risk for coronary artery disease in individuals with or without type 2 diabetes. Mol Genet Metab. 2004;81(4):282–90.

[29] Herrmann SM, R.S., Nicaud V, Mallet C, Arveiler D, Evans A, et al. Polymorphisms of the tumour necrosis factor-alpha gene, coronary heart disease. Eur J Clin Invest. 1998;28(1):59–66.

[30] Allen RA, L.E., Roberts DH, Park BK, Pirmohamed M. Polymorphisms in the TNF-α and TNF-receptor genes in patients with coronary artery disease. Eur J Clin Invest. 2001;31:843–51.

[31] Szalai C, F.G., Duba J, Kramer J, Romics L, Prohaszka Z, et al. Association of polymorphisms and allelic combinations in the tumour necrosis factor- alpha complement MHC region with coronary artery disease. J Med Genet. 2002;39(1):46–51.

[32] Furuta M, Y.Y., Ito K, Gabazza EC, Katsuki A, Tanaka T, et al. Relationship of the tumor necrosis factor-alpha -308 A/G promoter polymorphism with insulin sensitivity and abdominal fat distribution in Japanese patients with type 2 diabetes mellitus. Diabetes Res Clin Pract. 2002;56(2):141–45.

[33] Ackerman H, U.S., Mott R, Richardson A, Sisay-Joof F, Katundu P, et al. Haplotypic analysis of the TNF locus by association efficiency and entropy. Genome Biol.2003;4(4):R24.

[34] Cho HC, Y.G., Lee MY, Kim HS, Shin DH, Kim YN TNF-α polymorphisms and coronary artery disease: association study in the Korean population. Cytokine. 2013;62(1):104– 09.

[35] Day CP, G.J., Daly AK, Stewart MW, Avery PJ, Walker M. Tumour necrosis factor alpha gene promoter polymorphism and decreased insulin resistance. Diabetologia. 1998;41(4):430–34.

[36] Culpan D, M.S., Ford JM, Nicoll JA, Griffin WS, Dewar D, et al. Tumour necrosis factoralpha genepolymorphisms and Alzheimer’s disease. Neurosci Lett. 2003;350(1):61–65.