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Association of tumor necrosis factor-α (TNF-α) promoter polymorphisms with overweight/obesity in a Korean population

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Abstract

Objective

Obesity is characterized by the activation of an inflammatory process leading to an increase in proinflammatory cytokines and adipokines. This study was designed to investigate the genetic association between tumor necrosis factor-α (TNF-α) polymorphisms and the risk of obesity in the Korean population.

Methods

Three single nucleotide polymorphisms [G-238A (rs361525), C-857T (rs1799724), and C-863A (rs1800630)] in the promoter region of TNF-α gene were analyzed in 123 control [body mass index (BMI) between 18 and 23] and 208 overweight/obese (BMI ≥ 23) subjects.

Results

The mean values of BMI in the control and overweight/obese groups were 21.1 ± 1.4 and 25.4 ± 1.8, respectively. Of the three SNPs, G-238A presented a significant association with overweight/obesity in the codominant model; the frequency of the G/G genotype in the overweight/obese group was 9.3% higher than that in the control group (P = 0.0046). When control and overweight/obesity subjects were combined together and analyzed, the level of high-density lipoprotein (HDL) was significantly higher in the C-857T C/C type SNP (P < 0.05).

Conclusions

The results of this study suggest that the G allele of G-238A in TNF-α gene may be a risk factor for overweight/obesity in the Korean population and that the C allele of C-857T may be an protective factor in relation to the HDL level in the general Korean population.

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References

  1. Kopelman PG. Obesity as a medical problem. Nature. 2000;404:635–43.

    PubMed  CAS  Google Scholar 

  2. Wilson PWF, Grundy SM. The metabolic syndrome: practical guide to origins and treatment: Part I. Circulation. 2003;108:1422–5.

    Article  PubMed  Google Scholar 

  3. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–32.

    Article  PubMed  CAS  Google Scholar 

  4. Maes HHM, Neale MC, Eaves LJ. Genetic and environmental factor in relative body weight and human adiposity. Behav Genet. 1997;27:325–51.

    Article  PubMed  CAS  Google Scholar 

  5. Barsh GS, Farooqi IS, O’Rahilly S. Genetics of body-weight regulation. Nature. 2000;404:644–51.

    PubMed  CAS  Google Scholar 

  6. Rankinen T, Zuberi A, Chagnon YC, Weisnagel SJ, Argyropoulos G, Walts B, et al. The human obesity genemap: the 2005 update. Obesity. 2006;14:529–644.

    Article  PubMed  Google Scholar 

  7. Fantuzzi G. Leptin: nourishment for the immune system. Eur J Immunol. 2006;36:3101–4.

    Article  PubMed  CAS  Google Scholar 

  8. Feinstein R, Kanety H, Papa MZ, Lunenfeld B, Karasik A. Tumor necrosis factor-alpha suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates. J Biol Chem. 1993;268:26055–8.

    PubMed  CAS  Google Scholar 

  9. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259:87–91.

    Article  PubMed  CAS  Google Scholar 

  10. Sethi JK, Hotamisligil GS. The role of TNF-α in adipocyte metabolism. Semin Cell Dev Biol. 1999;10:19–29.

    Article  PubMed  CAS  Google Scholar 

  11. Hotamisligil G, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science. 1996;271:665–8.

    Article  PubMed  CAS  Google Scholar 

  12. Lang C, Dobrescu C, Bagby GJ. Tumor necrosis factor impairs insulin action on peripheral glucose disposal and hepatic glucose output. Endocrinology. 1992;130:43–52.

    Article  PubMed  CAS  Google Scholar 

  13. Feingold K, Grunfeld C. Tumor necrosis factor-alpha stimulates hepatic lipogenesis in the rat in vivo. J Clin Invest. 1987;80:184–90.

    Article  PubMed  CAS  Google Scholar 

  14. Stephens J, Pekala PH. Transcriptional repression of the GLUT4 and C/EBP genes in 3T3–L1 adipocytes by tumor necrosis factor-alpha. J Biol Chem. 1991;266:21839–45.

    PubMed  CAS  Google Scholar 

  15. Zhang B, Berger J, Hu E, Szalkowski D, White-Carrington S, Spiegelman BM, et al. Negative regulation of peroxisome proliferator-activated receptor-gamma gene expression contributes to the antiadipogenic effects of tumor necrosis factor-alpha. Mol Endocrinol. 1996;10:1457–66.

    Article  PubMed  CAS  Google Scholar 

  16. Feinstein R, Kanety H, Papa MZ, Lunenfeld B, Karasik A. Tumor necrosis factor-α suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates. J Biol Chem. 1993;268:26055–8.

    PubMed  CAS  Google Scholar 

  17. Stephens JM, Lee JL, Pilch PF. Tumor necrosis factor-α induced insulin resistance in 3T3–L1 adipocytes is accompanied by a loss of insulin receptor substrate-1 and glut4 expression without loss of insulin receptor-mediated signal transduction. J Biol Chem. 1997;272:971–6.

    Article  PubMed  CAS  Google Scholar 

  18. Skoog T, van’t Hooft FM, Kallin B, Jovinge S, Boquist S, Nilsson J, et al. A common functional polymorphism (C → A substitution at position –863) in the promoter region of the tumour necrosis factor-alpha (TNF-alpha) gene associated with reduced circulating levels of TNF-alpha. Hum Mol Genet. 1999;8:1443–9.

    Article  PubMed  CAS  Google Scholar 

  19. Kroeger K, Carville KS, Abraham LJ. The –308 tumor necrosis factor-alpha promoter polymorphism affects transcription. Mol Immunol. 1997;5:391–9.

    Article  Google Scholar 

  20. Kaluza W, Reuss E, Grossmann S, Hug R, Schopf RE, Galle PR, et al. Different transcriptional activity and in vitro TNF-alpha production inpsoriasis patients carrying the TNF-alpha 238A promoter polymorphism. J Invest Dermatol. 2000;114:1180–3.

    Article  PubMed  CAS  Google Scholar 

  21. Bayley J, de Rooij H, van den Elsen PJ, Huizinga TW, Verweij CL. Functional analysis of linker-scan mutants spanning the –376, –308, –244, and –238 polymorphic sites of the TNF-alpha promoter. Cytokine. 2001;14:316–23.

    Article  PubMed  CAS  Google Scholar 

  22. Higuchi T, Seki N, Kamizono S, Yamada A, Kimura A, Kato H, et al. Polymorphism of the 5′-flanking region of the human tumor necrosis factor (TNF)-alpha gene in Japanese. Tissue Antigens. 1998;51:605–12.

    Article  PubMed  CAS  Google Scholar 

  23. Koch M, Rett K, Volk A, Maerker E, Haist K, Weisser M, et al. 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. 2000;43:181–4.

    Article  PubMed  CAS  Google Scholar 

  24. Fernandez-Real J, Gutierrez C, Ricart W, Casamitjana R, Fernández-Castañer M, Vendrell J, et al. The TNF-alpha gene NcoI polymorphism influences the relationship among insulin resistance, percent body fat, and increased serum leptin levels. Diabetes. 1997;46:1468–72.

    Article  PubMed  CAS  Google Scholar 

  25. Day C, Grove J, Daly AK, Stewart MW, Avery PJ, Walker M. Tumour necrosis factor-alpha gene promoter polymorphism and decreased insulin resistance. Diabetologia. 1998;41:430–4.

    Article  PubMed  CAS  Google Scholar 

  26. Wybranska I, Malczewska-Malec M, Niedbal S, Naskalski JW, Dembinska-Kiec A. The TNF-alpha gene NcoI polymorphism at position –308 of the promoter influences insulin resistance, and increases serum triglycerides after postprandial lipaemia in familiar obesity. Clin Chem Lab Med. 2003;41:501–10.

    Article  PubMed  CAS  Google Scholar 

  27. Nicaud V, Raoux S, Poirier O, Cambien F, O’Reilly DS, Tiret L. The TNF alpha/G-308A polymorphism influences insulin sensitivity in offspring of patients with coronary heart disease: the European Atherosclerosis Research Study II. Atherosclerosis. 2002;161:317–25.

    Article  PubMed  CAS  Google Scholar 

  28. International Diabetes Institute. The Asia-Pacific perspective: redefining obesity and its treatment. Geneva: World Health Organization; 2000. p. 1–55.

    Google Scholar 

  29. World Health Organization. Obesity: preventing and managing the global epidemic. WHO obesity technical report series No. 894. Geneva: World Health Organization; 2000.

    Google Scholar 

  30. Choo V. WHO reassesses appropriate body-mass index for Asian populations. Lancet. 2002;360:235.

    Article  PubMed  Google Scholar 

  31. James WP, Chunming C, Inoue S. Appropriate Asian body mass indices? Obes Rev. 2002;3:139.

    Article  PubMed  CAS  Google Scholar 

  32. Hamminga EA, van der Lely AJ, Neumann HA, Thio HB. Chronic inflammation in psoriasis and obesity: implications for therapy. Med Hypotheses. 2006;67:768–73.

    Article  PubMed  CAS  Google Scholar 

  33. Nicaud V, Raoux S, Poirier O, Cambien F, O’Reilly DS, Tiret L. The TNF alpha/G-308A polymorphism influences insulin sensitivity in offspring of patients with coronary heart disease: the European Atherosclerosis Research Study II. Atherosclerosis. 2002;161:317–25.

    Article  PubMed  CAS  Google Scholar 

  34. Bennet AM, van Maarle MC, Hallqvist J, Morgenstern R, Frostegård J, Wiman B, et al. Association of TNF-alpha serum levels and TNFA promoter polymorphisms with risk of myocardial infarction. Atherosclerosis. 2006;187:408–14.

    Article  PubMed  CAS  Google Scholar 

  35. Romeo S, Sentinelli F, Capici F, Arca M, Berni A, Vecci E, et al. The G-308A variant of the Tumor Necrosis Factor-α (TNF-α) gene is not associated with obesity, insulin resistance and body fat distribution. BMC Med Genet. 2001;2:10.

    Article  PubMed  CAS  Google Scholar 

  36. Jae-Young Um, Jae-Hwang Park, Hyung-Min Kim. Gene polymorphisms in tumor necrosis factor locus and waist–hip ratio in obese Koreans. Clin Chim Acta. 2003;338(1-2):117–22.

    Article  Google Scholar 

  37. Baker RG, Hayden MS, Ghosh S. NF-κB, inflammation, and metabolic disease. Cell Metab. 2011;13(1):11–22.

    Article  PubMed  CAS  Google Scholar 

  38. Kaluza W, Reuss E, Grossmann S, Hug R, Schopf RE, Galle PR, Maerker-Hermann E, Hoehler T. Different transcriptional activity and in vitro TNF-alpha production in psoriasis patients carrying the TNF-alpha 238A promoter polymorphism. J Invest Dermatol. 2000;114(6):1180–3.

    Article  PubMed  CAS  Google Scholar 

  39. Yamashina M, Kaneko Y, Maesawa C, Kajiwara T, Ishii M, Fujiwara F, et al. Association of TNF-alpha gene promoter C-857T polymorphism with higher serum LDL cholesterol levels and carotid plaque formation in Japanese patients with type 2 diabetes. Tohoku J Exp Med. 2007;211(3):251–8.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Preventive Medicine, School of Medicine, Institute for Medical Genetics, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu, Korea

    Gyeong-Im Yu, In-Sung Chung & Dong-Hoon Shin

  2. Department of Biochemistry, School of Medicine, Institute for Medical Genetics, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu, Korea

    Eunyoung Ha

  3. Department of Physiology, School of Medicine, Chronic Disease Research Center, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu, Korea

    Sung-Hee Park, Jae-Hyung Park & Dae-Kyu Song

  4. Department of Physiology, School of Medicine, Institute for Medical Science, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu, Korea

    Jae-Hoon Bae

  5. Department of Home Economics Education, Kyungpook National University, Daegu, Korea

    Hyun-Sook Jang

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  1. Gyeong-Im Yu
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Correspondence to Eunyoung Ha or Dae-Kyu Song.

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Responsible Editor: Andras Falus.

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Yu, GI., Ha, E., Park, SH. et al. Association of tumor necrosis factor-α (TNF-α) promoter polymorphisms with overweight/obesity in a Korean population. Inflamm. Res. 60, 1099–1105 (2011). https://doi.org/10.1007/s00011-011-0372-z

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  • DOI: https://doi.org/10.1007/s00011-011-0372-z

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