Advertisement

Molecular Biology Reports

, Volume 41, Issue 9, pp 5805–5811 | Cite as

TNF A −308G>A polymorphism in Moroccan patients with type 2 diabetes mellitus: a case–control study and meta-analysis

  • Hajar Sefri
  • Houda Benrahma
  • Hicham Charoute
  • Fouzia Lakbakbi el yaagoubi
  • Hassan Rouba
  • Badiaa Lyoussi
  • Jalal Nourlil
  • Omar Abidi
  • Abdelhamid Barakat
Article

Abstract

Type 2 diabetes mellitus (T2DM) is one of causes of mortality and morbidity in Moroccan population. The identification of genes implicated in this disease can help to found a specific treatment and to improve the quality of life for type 2 diabetic patients. In this study we analyze the association between a polymorphism (−308G>A) of TNF A promoter gene and T2DM in Moroccan patients. Five hundred and fifty-one individuals (307 patients with T2DM and 244 controls) were genotyped for this polymorphism by PCR–RFLP. This association was further reconsidered by a meta-analysis on 21 studies including 8,187 cases and 7,811 controls. We found that in Moroccan patients the −308A allele is strongly associated with T2DM (p = 0.000002; odds ratio 1.79, 95 % confidence interval 1.41–2.28). Based on our meta-analysis, there was no significant association detected between the TNF A −308G>A polymorphism and risk for T2DM. Our results suggest that the −308G>A polymorphism is a genetic risk factor for the development of T2DM in Moroccan population. On the other hand the meta analysis results led to controversial conclusions in other ethnicities.

Keywords

TNF-α TNF A −308G>A polymorphism Type 2 diabetes mellitus Moroccan patients 

Notes

Acknowledgments

We acknowledge the family members involved in this study. This work was supported by Pasteur Institute of Morocco and a grant from the project NEPAD/NABNet (New Partnership for Africa’s Development, North Africa Biosciences Network).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11033_2014_3454_MOESM1_ESM.doc (53 kb)
Supplementary material 1 (DOC 53 kb)

References

  1. 1.
    International Diabetes Federation (2013) IDF Diabetes Atlas, 6th edn. Brussels, Belgium: International Diabetes Federation. http://www.idf.org/diabetesatlas
  2. 2.
    Permutt MA, Wasson J, Cox N (2005) Genetic epidemiology of diabetes. J Clin Invest 115:1431–1439PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Newman B, Selby JV, King MC, Slemenda C, Fabsitz R, Friedman GD (1987) Concordance for type 2 (non-insulin-dependent) diabetes mellitus in male twins. Diabetologia 30:763–768CrossRefPubMedGoogle Scholar
  4. 4.
    Lee SC, Pu YB, Chow CC, Yeung VT, Ko GT, So WY, Li JK, Chan WB, Ma RC, Critchley JA, Cockram CS, Chan JC (2000) Diabetes in Hong Kong Chinese: evidence for familial clustering and parental effects. Diabetes Care 23:1365–1368CrossRefPubMedGoogle Scholar
  5. 5.
    Hotamisligil GS (2006) Inflammation and metabolic disorders. Nature 444:860–867CrossRefPubMedGoogle Scholar
  6. 6.
    Dahlen E, Dawe K, Ohlsson L, Hedlund G (1998) Dendritic cells and macrophages are the first and major producers of tnf-alpha in pancreatic islets in the nonobese diabetic mouse. J Immunol 160:3585–3593PubMedGoogle Scholar
  7. 7.
    Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259:87–91CrossRefPubMedGoogle Scholar
  8. 8.
    Kubaszek A, Pihlajamäki J, Komarovski V, Lindi V, Lindström J, Eriksson J, Valle TT, Hämäläinen H, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Tuomilehto J, Uusitupa M, Laakso M (2003) Finnish diabetes prevention study. Promoter polymorphisms of the tnf-alpha (g-308a) and il-6 (c-174 g) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the finnish diabetes prevention study. Diabetes 52:1872–1876CrossRefPubMedGoogle Scholar
  9. 9.
    Zeggini E, Groves CJ, Parkinson JR, Halford S, Owen KR, Frayling TM, Walker M, Hitman GA, Levy JC, O’Rahilly S, Hattersley AT, McCarthy MI (2005) Large-scale studies of the association between variation at the tnf/lta locus and susceptibility to type 2 diabetes. Diabetologia 48:2013–2017CrossRefPubMedGoogle Scholar
  10. 10.
    Koch M, Rett K, Volk A, Maerker E, Haist K, Weisser M, Rettig A, Renn W, Häring HU (2000) The tumour necrosis factor alpha −238 g→a and −308 g→a promoter polymorphisms are not associated with insulin sensitivity and insulin secretion in young healthy relatives of type ii diabetic patients. Diabetologia 43:181–184CrossRefPubMedGoogle Scholar
  11. 11.
    Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW (1997) Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci USA 94:3195–3199PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Fernández-Real JM, Gutierrez C, Ricart W, Casamitjana R, Fernández-Castañer M, Vendrell J, Richart C, Soler J (1997) The tnf-alpha gene nco I polymorphism influences the relationship among insulin resistance, percent body fat, and increased serum leptin levels. Diabetes 46:1468–1472CrossRefPubMedGoogle Scholar
  13. 13.
    Herrmann SM, Ricard S, Nicaud V, Mallet C, Arveiler D, Evans A, Ruidavets JB, Luc G, Bara L, Parra HJ, Poirier O, Cambien F (1998) Polymorphisms of the tumour necrosis factor-alpha gene, coronary heart disease and obesity. Eur J Clin Invest 28:59–66CrossRefPubMedGoogle Scholar
  14. 14.
    Romeo S, Sentinelli F, Capici F, Arca M, Berni A, Vecci E, Di Mario U, Baroni MG (2001) The g-308a variant of the tumor necrosis factor-alpha (tnf-alpha) gene is not associated with obesity, insulin resistance and body fat distribution. BMC Med Genet 2:10PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Ishii T, Hirose H, Saito I, Nishikai K, Maruyama H, Saruta T (2000) Tumor necrosis factor alpha gene g-308a polymorphism, insulin resistance, and fasting plasma glucose in young, older, and diabetic Japanese men. Metabolism 49:1616–1618CrossRefPubMedGoogle Scholar
  16. 16.
    Walston J, Seibert M, Yen CJ, Cheskin LJ, Andersen RE (1999) Tumor necrosis factor-alpha-238 and -308 polymorphisms do not associated with traits related to obesity and insulin resistance. Diabetes 48:2096–2098CrossRefPubMedGoogle Scholar
  17. 17.
    Feng R, Li Y, Zhao D, Wang C, Niu Y, Sun C (2009) Lack of association between tnf 238 g/a polymorphism and type 2 diabetes: a meta-analysis. Acta Diabetol 46:339–343CrossRefPubMedGoogle Scholar
  18. 18.
    Benrahma H, Arfa I, Charif M, Bounaceur S, Eloualid A, Boulouiz R, Nahili H, Abidi O, Rouba H, Chadli A, Oudghiri M, Farouqui A, Abdelhak S, Barakat A (2011) Maternal effect and familial aggregation in a type 2 diabetic Moroccan population. J Community Health 36:943–948CrossRefPubMedGoogle Scholar
  19. 19.
    Benrahma H, Abidi O, Melouk L, Ajjemami M, Rouba H, Chadli A, Oudghiri M, Farouqui A, Barakat A (2012) Association of the c677t polymorphism in the human methylenetetrahydrofolate reductase (mthfr) gene with the genetic predisposition for type 2 diabetes mellitus in a Moroccan population. Genet Test Mol Biomark 16:383–387CrossRefGoogle Scholar
  20. 20.
    Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15(7):539–553CrossRefPubMedGoogle Scholar
  21. 21.
    Gustincich S, Manfioletti G, Del Sal G, Schneider C, Carninci P (1991) A fast method for high-quality genomic DNA extraction from whole human blood. Biotechniques 11(298–300):2Google Scholar
  22. 22.
    Hotamisligil GS, Spiegelman BM (1994) Tumor necrosis factor alpha: a key component of the obesity-diabetes link. Diabetes 43:1271–1278CrossRefPubMedGoogle Scholar
  23. 23.
    Feng RN, Zhao C, Sun CH, Li Y (2011) Meta-analysis of tnf 308 g/a polymorphism and type 2 diabetes mellitus. PLoS ONE 6:e18480PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    Deng GY, Maclaren NK, Huang HS, Zhang LP, She JX (1996) No primary association between the 308 polymorphism in the tumor necrosis factor alpha promoter region and insulin-dependent diabetes mellitus. Hum Immunol 45:137–142CrossRefPubMedGoogle Scholar
  25. 25.
    Bouhaha R, Baroudi T, Ennafaa H, Vaillant E, Abid H, Sassi R, Vatin V, Froguel P, Gaaied AB, Meyre D, Vaxillaire M (2010) Study of tnfalpha −308 g/a and il6 −174 g/c polymorphisms in type 2 diabetes and obesity risk in the Tunisian population. Clin Biochem 43:549–552CrossRefPubMedGoogle Scholar
  26. 26.
    Perez-Luque E, Malacara JM, Garay-Sevilla ME, Fajardo ME (2012) Association of the tnf-alpha −308 g/a polymorphism with family history of type 2 diabetes mellitus in a Mexican population. Clin Biochem 45:12–15CrossRefPubMedGoogle Scholar
  27. 27.
    Heijmans BT, Westendorp RG, Droog S, Kluft C, Knook DL, Slagboom PE (2002) Association of the tumour necrosis factor alpha −308 g/a polymorphism with the risk of diabetes in an elderly population-based cohort. Genes Immun 3:225–228CrossRefPubMedGoogle Scholar
  28. 28.
    Bayley JP, de Rooij H, van den Elsen PJ, Huizinga TW, Verweij CL (2001) Functional analysis of linker-scan mutants spanning the −376, −308, −244, and −238 polymorphic sites of the tnf-alpha promoter. Cytokine 14:316–323CrossRefPubMedGoogle Scholar
  29. 29.
    Kaluza W, Reuss E, Grossmann S, Hug R, Schopf RE, Galle PR, Maerker-Hermann E, Hoehler T (2000) Different transcriptional activity and in vitro tnf-alpha production in psoriasis patients carrying the tnf-alpha 238a promoter polymorphism. J Invest Dermatol 114:1180–1183CrossRefPubMedGoogle Scholar
  30. 30.
    Wajchenberg BL (2000) Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 21:697–738CrossRefPubMedGoogle Scholar
  31. 31.
    Hotamisligil GS, Murray DL, Choy LN, Spiegelman BM (1994) Tumor necrosis factor alpha inhibits signaling from the insulin receptor. Proc Natl Acad Sci USA 91:4854–4858PubMedCentralCrossRefPubMedGoogle Scholar
  32. 32.
    Feinstein R, Kanety H, Papa MZ, Lunenfeld B, Karasik A (1993) Tumor necrosis factor-alpha suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates. J Biol Chem 268:26055–26058PubMedGoogle Scholar
  33. 33.
    Kroder G, Bossenmaier B, Kellerer M, Capp E, Stoyanov B, Mühlhöfer A, Berti L, Horikoshi H, Ullrich A, Häring H (1996) Tumor necrosis factor-alpha- and hyperglycemia-induced insulin resistance. Evidence for different mechanisms and different effects on insulin signaling. J Clin Invest 97:1471–1477PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM (1996) Irs-1-mediated inhibition of insulin receptor tyrosine kinase activity in tnf-alpha- and obesity-induced insulin resistance. Science 271:665–668CrossRefPubMedGoogle Scholar
  35. 35.
    Guzmán-Flores JM, Muñoz-Valle JF, Sánchez-Corona J, Cobián JG, Medina-Carrillo L, García-Zapién AG, Cruz-Quevedo EG, Flores-Martínez SE (2011) Tumor necrosis factor-alpha gene promoter −308 g/a and −238 g/a polymorphisms in mexican patients with type 2 diabetes mellitus. Dis Markers 30:19–24PubMedCentralCrossRefPubMedGoogle Scholar
  36. 36.
    Shiau MY, Wu CY, Huang CN, Hu SW, Lin SJ, Chang YH (2003) Tnf-alpha polymorphisms and type 2 diabetes mellitus in Taiwanese patients. Tissue Antigens 61:393–397CrossRefPubMedGoogle Scholar
  37. 37.
    Furuta M, Yano Y, Ito K, Gabazza EC, Katsuki A, Tanaka T, Ohtake K, Hirata N, Hori Y, Araki-Sasaki R, Sumida Y, Adachi Y (2002) 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 56:141–145CrossRefPubMedGoogle Scholar
  38. 38.
    Hamann A, Mantzoros C, Vidal-Puig A, Flier JS (1995) Genetic variability in the tnf-alpha promoter is not associated with type II diabetes mellitus (niddm). Biochem Biophys Res Commun. 211:833–839CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Hajar Sefri
    • 1
  • Houda Benrahma
    • 1
  • Hicham Charoute
    • 1
  • Fouzia Lakbakbi el yaagoubi
    • 1
  • Hassan Rouba
    • 1
  • Badiaa Lyoussi
    • 2
  • Jalal Nourlil
    • 3
  • Omar Abidi
    • 1
  • Abdelhamid Barakat
    • 1
  1. 1.Laboratoire de Génétique Moléculaire Humaine, Département de Recherche ScientifiqueInstitut Pasteur du MarocCasablancaMorocco
  2. 2.Laboratory of Physiology, Department of Pharmacology and Environmental Health, Faculty of SciencesUniversity Sidi Mohamed Ben AbdallahFezMorocco
  3. 3.Medical Virology and BSL3 LaboratoryInstitut Pasteur du MarocCasablancaMorocco

Personalised recommendations