Skip to main content

Advertisement

Log in

Association of TNF-α-308 G>A (rs1800629) polymorphism with susceptibility of metabolic syndrome

  • Research article
  • Published:
Journal of Diabetes & Metabolic Disorders Aims and scope Submit manuscript

Abstract

Background

Metabolic Syndrome (MetS) mainly comprises hyperglycemia, hypertension and dyslipidemia, and has been proven to increase the risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease. Studies have suggested that many factors may be involved in the pathogenesis of MetS, but tumor necrosis factor alpha (TNF- α) may play a strong role as its gene polymorphism was associated with insulin resistance and obesity. The aim of this study was to evaluate the possible association of TNF-α-308 G > A (rs1800629) polymorphism with susceptibility of metabolic syndrome.

Methods

a case-control study was conducted upon 128 participants recruited from Suez Canal University Hospital (Ismailia, Egypt), divided into the MetS group (n = 64) and the control group (n = 64). Genotyping of the TNF-α-308 G > A (rs1800629) polymorphism was performed by restriction fragment length polymorphism (PCR-RFLP).

Results

The A allele was significantly higher among MetS patients (40%) than controls (11%) (p < 0.0001). A significant association was observed between the healthy and MetS groups under the influence of co-dominant, dominant and over-dominant genetic models (p < 0.05). Also, there were positive correlations between TNF-α-308 (G/A) polymorphism and risk factors of metabolic syndrome like body mass index (BMI); fasting blood sugar; cholesterol and low density lipoprotein (LDL) (p < 0.05). Regression analysis was done for predictors of MetS and the A allele was found to be a strong predictor (OR 2.752; 95% CI = 1.106 to 6.847; p = 0.03), as well as, BMI; triglyceride (TG); high density lipoprotein (HDL); LDL and cholesterol (p < 0.05).

Conclusions

TNF-α-308 G > A (rs1800629) polymorphism may be play an important role in the development of metabolic syndrome and A allele is a strong predictor in Egyptians.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112(17):2735–52.

    Article  Google Scholar 

  2. Stančáková A, Laakso M. Genetics of metabolic syndrome. Rev Endocr Metab Disord. 2014;15(4):243–52.

    Article  Google Scholar 

  3. Kaur J. A comprehensive review on metabolic syndrome. Cardiol Res Pract. 2014;2014:943162.

    PubMed  PubMed Central  Google Scholar 

  4. McCracken E, Monaghan M, Sreenivasan S. Pathophysiology of the metabolic syndrome. Clin Dermatol. 2018;36(1):14–20.

    Article  Google Scholar 

  5. Lau DC, Dhillon B, Yan H, Szmitko PE, Verma S. Adipokines: molecular links between obesity and atheroslcerosis. Am J Physiol Heart Circ Physiol. 2005;288(5):H2031–41.

    Article  CAS  Google Scholar 

  6. Lee SC, Pu YB, Thomas GN, Lee ZS, Tomlinson B, Cockram CS, et al. Tumor necrosis factor alpha gene G-308A polymorphism in the metabolic syndrome. Metab Clin Exp. 2000;49(8):1021–4.

    Article  CAS  Google Scholar 

  7. Srikanthan K, Feyh A, Visweshwar H, Shapiro JI, Sodhi K. Systematic review of metabolic syndrome biomarkers: a panel for early detection, management, and risk stratification in the west Virginian population. Int J Med Sci. 2016;13(1):25–38.

    Article  CAS  Google Scholar 

  8. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Maury E, Brichard SM. Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol. 2010;314(1):1–16.

    Article  CAS  Google Scholar 

  10. Wilson AG, de Vries N, Pociot F, di Giovine FS, van der Putte LB, Duff GW. An allelic polymorphism within the human tumor necrosis factor alpha promoter region is strongly associated with HLA A1, B8, and DR3 alleles. J Exp Med. 1993;177(2):557–60.

    Article  CAS  Google Scholar 

  11. Kabita S, Garg PR, Newmei MK, Saraswathy KN, Singh HSJJotPoCS. Tumor necrosis factor-alpha gene polymorphisms and complex disorders: A study among mendelian population with East Asian Ancestry 2019;5(1):35.

  12. 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.

    Article  CAS  Google Scholar 

  13. Arbab M, Tahir S, Niazi MK, Ishaq M, Hussain A, Siddique PM, et al. TNF-α genetic predisposition and higher expression of inflammatory pathway components in Keratoconus. Invest Ophthalmol Vis Sci. 2017;58(9):3481–7.

    Article  CAS  Google Scholar 

  14. Sookoian SC, González C, Pirola CJ. Meta-analysis on the G-308A tumor necrosis factor alpha gene variant and phenotypes associated with the metabolic syndrome. Obes Res. 2005;13(12):2122–31.

    Article  Google Scholar 

  15. You T, Nicklas BJ, Ding J, Penninx BW, Goodpaster BH, Bauer DC, et al. The metabolic syndrome is associated with circulating adipokines in older adults across a wide range of adiposity. J Gerontol Ser A Biol Sci Med Sci. 2008;63(4):414–9.

    Article  Google Scholar 

  16. Lann D, LeRoith D. Insulin resistance as the underlying cause for the metabolic syndrome. Med Clin North Am. 2007;91(6):1063–77 viii.

    Article  CAS  Google Scholar 

  17. Pyrzak B, Wiśniewska A, Rymkiewicz-Kluczyńska B. Tumor necrosis factor alpha (TNF-alpha) gene G-308A polymorphism relationship to insulin resistance and lipid abnormalities in children with obesity. Endokrynol Diabetol Chor Przemiany Materii Wieku Rozw. 2006;12(3):171–4.

    PubMed  Google Scholar 

  18. Ranjith N, Pegoraro RJ, Naidoo DP, Shanmugam R, Rom L. Genetic variants associated with insulin resistance and metabolic syndrome in young Asian Indians with myocardial infarction. Metab Syndr Relat Disord. 2008;6(3):209–14.

    Article  CAS  Google Scholar 

  19. Feng RN, Zhao C, Sun CH, Li Y. Meta-analysis of TNF 308 G/A polymorphism and type 2 diabetes mellitus. PLoS One. 2011;6(4):e18480.

    Article  CAS  Google Scholar 

  20. Voiculescu VM, Solomon I, Popa A, Draghici CC, Dobre M, Giurcaneanu C, et al. Gene polymorphisms of TNF-238G/A, TNF-308G/A, IL10-1082G/A, TNFAIP3, and MC4R and comorbidity occurrence in a Romanian population with psoriasis. J Med Life. 2018;11(1):69–74.

    PubMed  PubMed Central  Google Scholar 

  21. 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.

    Article  CAS  Google Scholar 

  22. Brown AE, Walker M. Genetics of insulin resistance and the metabolic syndrome. Curr Cardiol Rep. 2016;18(8):75.

    Article  Google Scholar 

  23. Banerjee M, Saxena M. Genetic polymorphisms of cytokine genes in type 2 diabetes mellitus. World J Diabetes. 2014;5(4):493–504.

    Article  Google Scholar 

  24. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640–5.

    Article  CAS  Google Scholar 

  25. Yang Y-H, Liu Y-Q, Zhang L, Li H, Li X-B, Ouyang Q, et al. Genetic polymorphisms of the TNF-α-308G/A are associated with metabolic syndrome in asthmatic patients from Hebei province, China. Int J Clin Exp Pathol. 2015;8(10):13739–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Szkup M, Chełmecka E, Lubkowska A, Owczarek AJ, Grochans E. The influence of the TNFα rs1800629 polymorphism on some inflammatory biomarkers in 45-60-year-old women with metabolic syndrome. Aging (Albany NY). 2018;10(10):2935–43.

    Article  CAS  Google Scholar 

  27. Stein CM, Song Y, Elston RC, Jun G, Tiwari HK, Iyengar SK. Structural equation model-based genome scan for the metabolic syndrome. BMC Genet. 2003;4(Suppl 1):S99.

    Article  Google Scholar 

  28. Peng Y, Li LJ. TNF-α-308G/A polymorphism associated with TNF-α protein expression in patients with diabetic nephropathy. Int J Clin Exp Pathol. 2015;8(3):3127–31.

    PubMed  PubMed Central  Google Scholar 

  29. Pausova Z, Sedova L, Berube J, Hamet P, Tremblay J, Dumont M, et al. Segment of rat chromosome 20 regulates diet-induced augmentations in adiposity, glucose intolerance, and blood pressure. Hypertension. 2003;41(5):1047–55.

    Article  CAS  Google Scholar 

  30. de Luis DA, Aller R, Izaola O, González Sagrado M, Conde R, Romero E. Influence of G308A polymorphism of tumor necrosis factor alpha gene on insulin resistance in obese patients after weight loss. Med Clin (Barc). 2007;129(11):401–4.

    Article  Google Scholar 

  31. Li Y-yJPO. Tumor necrosis factor-alpha g308α gene polymorphism and essential hypertension: a meta-analysis involving 2244 participants. 2012;7(4):e35408.

  32. Zafar U, Khaliq S, Ahmad HU, Lone KP. Serum profile of cytokines and their genetic variants in metabolic syndrome and healthy subjects: a comparative study. Biosci Rep. 2019;39(2).

Download references

Funding

This work was done by own author funding.

Author information

Authors and Affiliations

Authors

Contributions

All authors have participated in the study.

Corresponding author

Correspondence to Dalia Ghareeb.

Ethics declarations

Author disclosures

The authors declare that they have no conflict of interest.

Consent to participate

All the patients were informed about the research and verbal informed consent was obtained prior to the interview.

Ethical approval

This research has been approved by the Medical Research Ethics Committee of the Suez Canal University Faculty of Medicine (Ismailia, Egypt) and the study has been conducted according to the principles expressed in the Helsinki Declaration.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Key messages

• There is an evidence indicates that TNF-α 308 (G/A) polymorphism may participate in development of metabolic syndrome.

• The A allele was found to be a strong predictor as well as, BMI; TG; HDL; LDL and cholesterol for susceptibility of metabolic syndrome in Egyptian patients.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ghareeb, D., Abdelazem, A.S., Hussein, E.M. et al. Association of TNF-α-308 G>A (rs1800629) polymorphism with susceptibility of metabolic syndrome. J Diabetes Metab Disord 20, 209–215 (2021). https://doi.org/10.1007/s40200-021-00732-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40200-021-00732-3

Keywords

Navigation