Association between Metabolic Syndrome and the Polymorphism of TNF-a-308 G>A Gene in Kerman, Iran

Document Type : Original article

Authors

1 Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

2 Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology sciencesSciences, Kerman University of Medical Sciences, Kerman, Iran.

3 Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

4 Department of Gastroenterology, Afzalipour hospital, Kerman University of Medical Sciences, Kerman, Iran.

Abstract

Introduction: Metabolic syndrome (MetS) is currently prevalent in adults. The main clinical symptoms of MetS include central obesity, hyperglycemia, high triglycerides, low high-density lipoprotein levels, and hypertension. Genetic factors play an important role in the development of MetS. The present study aimed to evaluate the correlation between two gene polymorphisms, including TNF-a -308 G>A (rs 1800629) and IL-6 -174 G>C (rs1800795) with MetS and its components.
Materials and Methods: This case-control study included 250 participants who were assigned into the case group with MetS (n=125) and control group (n=125). The mean ages of males in the case and control groups were 54.5 and 39.44 years, respectively. Moreover, the mean ages of females in the case and control groups were 53.05 and 33.69 years, respectively. In addition, the number of male and female in the case group was 40 (32%) and 85 (68%), respectively. Additionally, 43 (34.4%) and 82 (65.6%) males and females participated in the control group, respectively. There was no significant difference between the groups regarding gender (P=0.842). In this study, DNA was extracted from the blood, and Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was employed to detect two gene polymorphisms, including TNF-a -308 G>A and IL-6 -174 G>C among participants.
Results: The results obtained from this study showed a significant association between TNF-a-308 G>A and MetS (P<0.05). However, there was no significant association between IL-6 174 G>C and MetS. Additionally, no association was observed between MetS components and the aforementioned polymorphisms.
Conclusion: According to the results, an association was observed between TNF-a-308 G>A gene polymorohism and MetS.

Keywords


  1. Rochlani Y, Pothineni NV, Kovelamudi S, Mehta JL. Metabolic syndrome: pathophysiology, management, and modulation by natural compounds. Ther Adv Cardiovasc Dis. 2017; 11(8):215-25.
  2. Alberti KG, Zimmet P, Shaw J. Metabolic syndrome--a new world‐wide definition. A consensus statement from the international diabetes federation. Diabetic Med. 2006; 23(5):469-80.
  3. Kawamoto R, Tabara Y, Kohara K, Miki T, Kusunoki T, Takayama S, et al. Relationships between lipid profiles and metabolic syndrome, insulin resistance and serum high molecular adiponectin in Japanese community-dwelling adults. Lipids Health Dis. 2011; 10(1):79.
  4. Carey RM, Whelton PK. Prevention, detection, evaluation, and management of high blood pressure in adults: synopsis of the 2017 American College of Cardiology/American Heart Association Hypertension Guideline. Ann Intern Med. 2018; 168(5):351-8.
  5. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010; 33(Suppl 1):S62-9.
  6. Nakayama Y, Komuro R, Yamamoto A, Miyata Y, Tanaka M, Matsuda M, et al. RhoA induces expression of inflammatory cytokine in adipocytes. Biochem Biophys Res Commun. 2009; 379(2):288-92.
  7. Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, et al. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw. 2006; 17(1):4-12.
  8. Kirk EA, Sagawa ZK, McDonald TO, O'Brien KD, Heinecke JW. Monocyte chemoattractant protein-1 deficiency fails to restrain macrophage infiltration into adipose tissue. Diabetes. 2008; 57(5):1254-61.
  9. Dandona P, Aljada A, Chaudhuri A, Mohanty P, Garg R. Metabolic syndrome: a comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation. 2005; 111(11):1448-54.
  10. Esmaillzadeh A, Azadbakht L. Increased levels of inflammation among women with enlarged waist and elevated triglyceride concentrations. Ann Nutr Metab. 2010; 57(2):77-84.
  11. Williams KJ, Tabas I. Atherosclerosis and inflammation. Science. 2002; 297(5581):521-2.
  12. Mazloomzadeh S, Khazaghi ZR, Mousavinasab N. The prevalence of metabolic syndrome in Iran: a systematic review and meta-analysis. Iran J Public Health. 2018; 47(4):473-80.
  13. Wu H, Ballantyne CM. Skeletal muscle inflammation and insulin resistance in obesity. J Clin Invest. 2017; 127(1):43-54.
  14. Swaroop JJ, Rajarajeswari D, Naidu J. Association of TNF-α with insulin resistance in type 2 diabetes mellitus. Indian J Med Res. 2012; 135(1):127-30.
  15. Mohammadi M, Gozashti MH, Aghadavood M, Mehdizadeh MR, Hayatbakhsh MM. Clinical significance of serum IL-6 and TNF-α levels in patients with metabolic syndrome. Rep Biochem Mol Biol. 2017; 6(1):74-9.
  16. Sarbijani HM, Khoshnia M, Marjani A. The association between metabolic syndrome and serum levels of lipid peroxidation and interleukin-6 in Gorgan. Diabetes Metab Syndr. 2016; 10(1):S86-9.
  17. Lukic L, Lalic N, Rajkovic N, Jotic A, Lalic K, Milicic T, et al. Hypertension in obese type 2 diabetes patients is associated with increases in insulin resistance and IL-6 cytokine levels: potential targets for an efficient preventive intervention. Int J Environ Res Public Health. 2014; 11(4):3586-98.
  18. Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW. Effects of a polymorphism in the human tumor necrosis factor α promoter on transcriptional activation. Proc Natl Acad Sci. 1997; 94(7):3195-9.
  19. Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S, et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest. 1998; 102(7):1369-76.
  20. Vikram NK, Bhatt SP, Bhushan B, Luthra K, Misra
    A, Poddar PK, et al. Associations of-308G/A polymorphism of tumor necrosis factor (TNF)–α gene and serum TNF-α levels with measures of obesity, intra-abdominal and subcutaneous abdominal fat, subclinical inflammation and insulin resistance in Asian Indians in North India. Disease Markers. 2011; 31(1):39-46.
  21. Gupta V, Gupta A, Jafar T, Gupta V, Agrawal S, Srivastava N, et al. Association of TNF-α promoter gene G-308A polymorphism with metabolic syndrome, insulin resistance, serum TNF-α and leptin levels in Indian adult women. Cytokine. 2012; 57(1):32-6.
  22. Golshani H, Haghani K, Dousti M, Bakhtiyari S. Association of TNF-α 308 G/A polymorphism with type 2 diabetes: a case–control study in the Iranian Kurdish Ethnic Group. Osong Public Health Res Perspect. 2015; 6(2):94-9.
  23. Ma H, Sun G, Wang W, Zhou Y, Liu D, Tong Y, et al. Association between interleukin-6-572 C> G and-174 G> C polymorphisms and hypertension: a meta-analysis of case-control studies. Medicine. 2016; 95(2):e2416.
  24. Boeta‐Lopez K, Duran J, Elizondo D, Gonzales E, Rentfro A, Schwarzbach A, et al. Association of interleukin-6 polymorphisms with obesity or metabolic traits in young Mexican‐Americans. Obes Sci Pract. 2018; 4(1):85-96.
  25. Despotovic M, Stoimenov TJ, Stankovic I, Pavlovic D, Sokolovic D, Cvetkovic T, et al. Gene polymorphisms of tumor necrosis factor alpha and antioxidant enzymes in bronchial asthma. Adv Clin Exp Med. 2015; 24(2):251-6.
  26. Białecka M, Jurewicz A, Machoy-Mokrzyńska A, Kurzawski M, Leźnicka K, Dziedziejko V, et al. Effect of interleukin 6–174G> C gene polymorphism on opioid requirements after total hip replacement. J Anesth. 2016; 30(4):562-7.
  27. Pausova Z, Deslauriers B, Gaudet D, Tremblay J, Kotchen TA, Larochelle P, et al. Role of tumor necrosis factor-α gene locus in obesity and obesity-associated hypertension in French Canadians. Hypertension. 2000; 36(1):14-9.
  28. Wingeyer SDP, Graffigna MN, Belli SH, Benetucci J, de Larranaga GF. Role of-675 4G/5G in the plasminogen activator inhibitor-1 gene and-308g/a tumor necrosis factor-α gene polymorphisms in obese argentinean patients. Genet Test Mol Biomarkers. 2012; 16(5):372-5.
  29. Hedayati M, Sharifi K, Rostami F, Daneshpour M, Yeganeh MZ, Azizi F. Association between TNF-α promoter G-308A and G-238A polymorphisms and obesity. Mol Biol Rep. 2012; 39(2):825-9.
  30. Mărginean CO, Mărginean C, Iancu M, Moldovan VG, Melit LE, Bănescu C. The impact of TNF-α 308G> a gene polymorphism on children’s overweight risk and an assessment of biochemical variables: a cross-sectional single-center experience. Pediatr Neonatol. 2019; 60(1):19-27.
  31. Stephens JW, Hurel SJ, Lowe GD, Rumley A, Humphries SE. Association between plasma IL-6, the IL6− 174G> C gene variant and the metabolic syndrome in type 2 diabetes mellitus. Mol Genet Metab. 2007; 90(4):422-8.
  32. Teixeira AA, Quinto BM, Dalboni MA, Rodrigues CJ, Batista MC. Association of IL-6 polymorphism-174G/C and metabolic syndrome in hypertensive patients. Biomed Res Int. 2015; 2015:927589.