Correlation of STAT4 gene Polymorphism (rs3024839) with risk of myocardial infarction (MI)

Document Type : Research Paper

Authors

1 Department of Genetics, Colleague of Science, Kazerun branch, Islamic Azad University, Kazerun, Iran

2 Department of Genetics, Colleague of Science, Kazerun branch, Islamic Azad University, Kazerun, Iran.

Abstract

Background: The studies have demonstrated that Signal transduction and activation of transcription (STATs) play a major role in atherosclerotic plaque disruption and lead to myocardial infarction (MI). The present study was done to investigate the association between the STAT4 gene polymorphism in site of rs3024839 with the risk of developing MI in an Iranian population.
Material and Methods: This is a case-control study. The possible association between STAT4 polymorphism (SLC6A4) with the development of MI was investigate in a group of 200 patients with a history of MI and 200 healthy controls. The two groups were matched in terms of TCe and sex. After DNA extraction and replication, Genotypes and alleles frequency were determined in two groups using polymerase chain reaction (PCR-ARMS). The results were analyzed by SPSS software using Chi-square and logistic regression tests.
Finding: The result showed a significant difference in the rates of TC STAT4 genotype between MI and control groups (p=0.03). There was not any significant relationship between STAT4 gene polymorphisms and risk factor of MI such as sex, hypertension, dyslipidemia, diabetes, type of MI (STEMI or NSTEMI) (P>0.05).
Conclusion: The results of presented study reveal that the rs3024839 T/C polymorphism of the STAT4 gene probably plays a specific role in the risk of developing MI in Iranian population. But, further well-designed studies with large sample sizes are required to confirm our results.

Keywords


  1. Wang S, Dai YX, Chen LL, Jiang T, Zheng MQ, Li CG, et al. Effect of IL-1β, IL-8, and IL-10 polymorphisms on the development of myocardial infarction. Genet Mol Res. 2015; 14(4): 12016-12021.
  2. Kaur R, Das R, Ahluwalia J, Kumar RM, Talwar KK. Genetic polymorphisms, Biochemical Factors, and Conventional Risk Factors in Young and Elderly North Indian Patients with Acute Myocardial Infarction. Clin Appl Thromb Hemost. 2016 Mar;22(2):178-83.
  3. World Health Organization. Global status report on noncommunicable disaeses. Geneva: World Health Organization; 2011.
  4. Venkateshwarlu M, Gayathri C. Study of signifcance of estimation of lipid profle in patient with acute myocardial infarction. Int J Inf Res Rev. 2015; 2:1028–1030.
  5. Wang Y-L, Sun L-M, Zhang L, et al. Association between Apolipoprotein E polymorphism and myocardial infarction risk: A systematic review and meta-analysis. FEBS Open Bio. 2015; 5:852-858.
  6. Rodríguez-Pérez JM, Vargas-Alarcón G, Posadas-Sánchez R, ZTCal-Jiménez TX, Ortíz-Alarcón R, Valente-Acosta B, et al. rs3918242 MMP9 gene polymorphism is associated with myocardial infarction in Mexican patients. Genet Mol Res. 2016 Mar 4;15(1):15017776.
  7. Rathore V, Singh N, Mahat RK. Risk Factors for Acute Myocardial Infarction. EJMI. 2018;2(1):1–7. doi: 10.14744/ejmi.2018.76486
  8. Huma S, Tariq R, Amin F, Mahmood KT. Modifiable and non-modifiable predisposing risk factors of myocardial infarction -A review. J Pharm Sci Res. 2012; 4:1649-1653.
  9. Dogra RK, Das R, Ahluwalia J, Kumar RM, Talwar KK. Prothrombotic gene polymorphisms and plasma factors in young north Indian survivors of acute myocardial infarction. J Thromb Thrombolysis. 2012;34(2):276-282.
  10. Kaur R, Das R, Ahluwalia J, Kumar RM, Talwar KK. Synergistic effect of angiotensin II type-1 receptor 1166A/C with angiotensin-converting enzyme polymorphism on risk of acute myocardial infarction in north Indians. J Renin Angiotensin Aldosterone Syst. 2012;13(4):440-445.
  11. Dai X, Wiernek S, Evans JP, Runge MS. Genetics of coronary artery disease and myocardial infarction. World J Cardiol. 2016; 8(1): 1-23 Available from dio: http://dx.doi.org/10.4330/wjc.v8.i1.1
  12. SzelTC M, Piaszyk-Borychowska A, Plens-Galaska M, Wesoly J, Bluyssen HAR. Targeted inhibition of STATs and IRFs as a potential treatment strategy in cardiovascular disease. Oncotarget. 2016;7(30):48788-48812.
  13. Dąbrowska-Żamojcin E, Dziedziejko V, Safranow K, Domański L, Słuczanowska-Głabowska S, Pawlik A. STAT4 gene polymorphism in patients after renal allograft transplantation. Cent Eur J Immunol. 2016;41(3):255-259.
  14. Kishore R, Verma SK. Roles of STATs signaling in cardiovascular diseases. JAK-STAT. 2012;1(2):118-124.
  15. Levy DE, Darnell JE Jr. STATs: transcriptional control and biological impact. Nat Rev Mol Cell Biol. 2002; 3:651-662.
  16. Kaplan MH. STAT4: a critical regulator of inflammation in vivo. Immunol Res. 2005; 31: 231-242.
  17. O’Malley JT, Sehra S, Thieu VT, et al. Signal transducer and activator of transcription 4 limits the development of adaptive regulatory T cells. Immunology. 2009; 127: 587-595.
  18. Salmaninejad A, Mahmoudi M, Aslani S, Poursani S, Ziaee V, Rezaei N. Association of STAT4 gene single nucleotide polymorphisms with Iranian juvenile-onset systemic lupus erythematosus patients. Turk J Pediatr. 2017;59(2):144-149.
  19. Bi C, Li B, Cheng Z, Hu Y, Fang Z, Zhai A. Association study of STAT4 polymorphisms and type 1 diabetes in Northeastern Chinese Han population. Tissue Antigens. 2013 Mar;81(3):137-40.
  20. Zhao Y, Liu X, Liu X, Li Y, Zhang X, Zhu L, et al. Association of STAT4 gene polymorphism with increased susceptibility of rheumatoid arthritis in a northern Chinese Han subpopulation. Int J Rheum Dis. 2013; 16:178-184.
  21. Liu QF, Li Y, Zhao QH, et al. Association of STAT4 rs7574865 polymorphism with susceptibility to inflammatory bowel disease: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2015; 39: 627-636.
  22. Svenungsson E, Gustafsson J, Leonard D, et al. A STAT4 risk allele is associated with ischaemic cerebrovascular events and anti-phospholipid antibodies in systemic lupus erythematosus. Ann Rheum Dis. 2010; 69:834-40.
  23. Hansson GK. Infl ammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005; 352:1685–95.
  24. Leonard D, Svenungsson E, Dahlqvist J, Alexsson A, Ärlestig L, Taylor KE, et al. Novel gene variants associated with cardiovascular disease in systemic lupus erythematosus and rheumatoid arthritis. Ann Rheum Dis. 2018 Jul;77(7):1063-1069.
  25. Fu K, Peng Y, Li YJ, Xie Q, Yang H, Zhou B, Rao L. Signal transducer and activator of transcription 4 gene polymorphisms associated with dilated cardiomyopathy in Chinese Han population. Sichuan Da Xue Xue Bao Yi Xue Ban. 2013 Jul;44(4):558-62.
  26. Dobrian AD, Hatcher MA, Brotman JJ, Galkina EV, TTChavie-Moghadam P, Pei H, et al. STAT4 contributes to adipose tissue inflammation and atherosclerosis. J Endocrinol. 2015 Oct;227(1):13-24.
  27. Sperati CJ, Parekh RS, Berthier-Schaad Y, Jaar BG, Plantinga L, Fink N, et al. Association of single-nucleotide polymorphisms in JAK3, STAT4, and STAT6 with new cardiovascular events in incident dialysis patients. Am J Kidney Dis. 2009 May;53(5):845-55. doi: 10.1053/j.ajkd.2008.12.025. Epub 2009 Mar 12.