Year 2020, Volume 6 , Issue 5, Pages 422 - 428 2020-09-04

Investigation of the relationship between atherosclerosis and interleukin-6 -174G⁄C gene polymorphism

Umut Serhat SANRI [1]


Objectives: Atherosclerosis is a chronic disease that causes various cardiovascular complications. The onset and progression of atherosclerosis depends primarily on genetic factors and life style, but the underlying cellular and molecular mechanisms are still unclear. In recent studies, circulating cytokines have been shown to play an important role in inflammatory events. Interleukin-6 (IL-6) plays an important role in the regulation of proinflammation. In this study, a single nucleotide polymorphism of IL-6 gene at position -174 was studied. Our aim was to investigate the relationship between IL-6 -174G/C polymorphism and atherosclerosis.

Methods: In this prospective randomized study, 104 patients were included in both groups. We used Polymerase Chain Reaction-Restriction Fragment Lenght Polymorphism (PCR-RFLP) method to amplify the polymorphism region.

Results: Allele frequency distributions of IL-6 -174G/C polymorphism in the study and control groups were evaluated. There were no statistically significant diversity between A and B allele frequencies.

Conclusions: The allele frequency and genotype distribution between the groups was not statistically different, which indicates another mechanisms on regulation of these cytokines. Single gene polymorphisms are generally not reproducible. Therefore, broad-based studies should be carried out considering suitable conditions and multi-factor features. 

Coronary atherosclerosis, IL-6 gene polymorphism, risk factors
  • 1. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002;105:1135-43.
  • 2. Resncik HE, Howard EV. Diabetes and cardiovascular disease. Annu Rev Med 2002;53:245-67.
  • 3. Ridker PM. Clinical application of CRP for cardiovascular disease detection and prevention. Circulation 2003;107:363-9.
  • 4. Christopher KG, Joseph LW. Atherosclerosis: the road ahead. Cell 2001;104:503-16.
  • 5. Borish L, Steinke JW. Cytokines and chemokines. J Allergy Clin Immunol 2003;111:460-75.
  • 6. Heinrich PC, Behrmann I, Haan S, Hermanns HM, Müller-Newen G, Schaper F. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 2003;374(Pt 1):1-20.
  • 7. Kishimoto T. Interleukin-6: discovery of a pleiotropic cytokine. Arthritis Res Ther 2006;8 Suppl 2:S2.
  • 8. Morgan L, Cooper J, Montgomery H, Kitchen N, Humphries SE. The interleukin-6 gene -174G>C and -572G>C promoter polymorphisms are related to cerebral aneurysms. J Neurol Neurosurg Psychiatry 2006;77:915-7.
  • 9. Vakili H, Ghaderian SMH, Najar RA, Panah AST, Azargashb E. Genetic polymorphism of interleukin-6 gene and susceptibility to acute myocardial infarction. Coron Artery Dis 2011;22:299-305.
  • 10. Ma Y, Tang RK, Yang X, Peng GG, Liu Y, Wang XM, et al. Lack of an association between interleukin-6 gene promoter polymorphisms (-174G/C, - 572G/C) and ischemic heart disease and/or ischemic stroke: a meta-analysis. Hum Immunol 2011;72:641-51.
  • 11. Liu Y, Berthier-Schaad Y, Fallin MD, Fink NE, Tracy RP, Klag MJ, et al. IL-6 haplotypes, inflammation, and risk for cardiovascular disease in a multiethnic dialysis cohort. J Am Soc Nephrol 2006;17:863-70.
  • 12. Sambrook J, Fritsch EF, Maniatis T. Molecular Cloning: a laboratory manual. 2nd ed. N.Y., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, 1989: p. 1659.
  • 13. Gisterå A, Hansson GK. The immunology of atherosclerosis. Nat Rev Nephrol 2017;13:368-80.
  • 14. Uyemura K, Demer LL, Castle SC, Jullien D, Berliner JA, Gately MK, et al. Cross-regulatory roles of interleukin (IL)-12 and IL-10 in atherosclerosis. J Clin Invest 1996;97:2130-8.
  • 15. Kishimoto T. The biology of interleukin-6. Blood 1989;74:1-10.
  • 16. Tousoulis D, Oikonomou E, Economou EK, Crea F, Kaski JC. Inflammatory cytokines in atherosclerosis: current therapeutic approaches, Eur Heart J 2016;37:1723-32.
  • 17. Harismendy O, Notani D, Song X, Rahim RG, Tanasa B, Heintzman N, et al. 9p21 DNA variants associatedwith coronary arterydisease impair interferon-gammasignalling response. Nature 2011;470:264-8.
  • 18. Lusis AJ. Genetics of atherosclerosis. Trends Genet 2012;28:267-75.
  • 19. Francis SE, Camp NJ, Burton AJ, Dewberry RM, Gunn J, Stephens-Lloyd A, et al. Interleukin 1 receptor antagonist gene polymorphism and coronary artery disease. Circulation 1999;99:861-6.
  • 20. Kastrati A, Koch W, Berger PB, Mehilli J, Stephenson K, Neumann FJ, et al. Protective role against restenosis from an interleukin -1 receptor antagonist gene polymorphism in patients treated with coronary stenting. J Am Coll Cardiol 2000;362168-73.
  • 21. Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys MB, et al. The prognostic value of C-reactive protein and serum amyloid A protein in severe unstable angina. N Engl J Med 1994;331:417-24.
  • 22. Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW. C reactive protein in healthy subjects: associations with obesity, insulin resistance and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Atheroscler Thromb Vasc Biol 1999;19:972-8.
  • 23. Losito A, Kalidas K, Santoni S, Jeffery S. Association of interleukin-6 - 174G/C promoter polymorphism with hypertension and left ventricular hypertrophy in dialysis patients. Kidney Int 2003;64:616-22.
  • 24. Yamada T, Okuda Y, Itoh Y. The frequency of serum amyloid A2 alleles in the Japanese population. Amyloid 1998;5:208-11.
  • 25. Foster CB, Zhu S, Erichsen HC, Lehrnbecher T, Hart ES, Choi E, et al. Early Chronic ITP Study Group. Polymorphisms in inflammatory cytokines and Fcgamma in childhood chronic immune thrombocytopenic purpura: a pilot study. Br J Haematol 2001;113:596-99.
Primary Language en
Subjects Cardiac and Cardiovascular Systems
Journal Section Original Articles
Authors

Orcid: 0000-0003-4008-4336
Author: Umut Serhat SANRI (Primary Author)
Institution: Department of Cardiovascular Surgery, University of Health Sciences, Bursa Yüksek İhtisas Training and Research Hospital, Bursa, Turkey
Country: Turkey


Supporting Institution Cumhuriyet University Scientific Research Projects .
Project Number CÜBAP Project No: T-482
Thanks I would like to express my gratitude to Dr. Serdal ARSLAN who provided technical support and assistance in terms of information and methods for DNA isolation and screening of the selected gene region.
Dates

Application Date : December 24, 2019
Acceptance Date : January 30, 2020
Publication Date : September 4, 2020

EndNote %0 The European Research Journal Investigation of the relationship between atherosclerosis and interleukin-6 -174G⁄C gene polymorphism %A Umut Serhat Sanrı %T Investigation of the relationship between atherosclerosis and interleukin-6 -174G⁄C gene polymorphism %D 2020 %J The European Research Journal %P -2149-3189 %V 6 %N 5 %R doi: 10.18621/eurj.664078 %U 10.18621/eurj.664078