The Association between IL6-174 G/C Gene Polymorphism and Obesity: A Systematic Review and Meta-analysis


1 Assistant Professor, Department of Physical education and sport sciences, Faculty of literature and Humanities, Lorestan University, Khoramabad, Iran. E-mail: Tel: 09124525538

2 Master of science, Department of Physical education and sport sciences, Faculty of literature and Humanities, Lorestan University, Khoramabad, Iran

3 Assistant Professor, Department of Physical education and sport sciences, Faculty of literature and Humanities, Lorestan University, Khoramabad, Iran


Background: The interaction between genetic and environmental factors has resulted in growing prevalence of obesity around the world. IL6-174 G/Cgene polymorphism is widely studied as the involved factor in developing obesity. Objectives: The aim of the present study is to evaluate the relationship between Interleukin 6-174 G/C promoter gene polymorphism and obesity in a systematic review and meta-analysis study. Methods: In the present study Science Direct,Medline, Embase, Google Scholar, PubMedand SID search engines have been searched until March 2016. Articles were evaluated using the key words IL6 plus polymorphism or mutation or variant and adiposity, BMI and obesity. Data was analyzed using STATA software (12th version). OR ratio was calculated with 95% confidence interval to evaluate the strength in link between IL6 gene and obesity. Heterogeneity was calculated using I2 test. Articles bias was evaluated using funnel plot versus standard error (SE). The asymmetrydegree of the funnel plot was tested using linear regression tests ofEgger's and Begg's. Results: Generally, 12 articles entered systematic review and 6 articles entered final meta-analysis. After data was extracted, the total case group consisted of 5343 people and control group consisted of 3449 people. The odds ratio was estimated for additive model CC vs GC (OR= 1; CI: 95%: 0/9-1/12), recessive model CC + GC vs GG (OR= 1/04; CI: 95%: 0/95- 1/15) and for dominant model (OR= 1/10; CI: 95%: 1-1/21). Also the results showed that there is a statistically significant relationship between IL-61-74 G/C gene polymorphism and obesity (P


  1. Yanovski SZ, Yanovski JA, Alstair JJ. Drug therapy. N Engl J Med. 2002;346(8):591-602.
  2. Barsh  GS,  Farooqi  IS,  O'rahilly  S.  Genetics  of  body-weight regulation. Nature. 2000;404(6778):644-51. doi: 10.1038/ 35007519. [PubMed: 10766251].
  3. Lewis JP, Shuldiner AR. Genetics of the metabolic complications of obesity. Prog Mol Biol Transl Sci. 2009;94:349-72. doi: 10.1016/B978-0-12-375003-7.00012-1. [PubMed: 21036331].
  4. Hauner H. Secretory factors from human adipose  tissue and their functional role. Proc Nutr Soc. 2005;64(2):163-9. [PubMed: 15960861].
  5. Rostami  F,  Hosseini  R,  Sharifi  K,  Daneshpour  M,  Azizi  F, Hedayati  M.  Association  of  G-174C  polymorphism  of  the interleukin-6 gene promoter with obesity in Iranian population. Int J Med Health Sci. 2010;4(9):400-3. doi: 10.5281/zenodo.1071988.
  6. Qi  L,  Zhang  C,  van  Dam  RM,  Hu  FB.  Interleukin-6  genetic variability and adiposity: associations in two prospective cohorts and systematic review in 26,944 individuals. J Clin Endocrinol Metab. 2007;92(9):3618-25. doi: 10.1210/jc.2007- 0877. [PubMed: 17623760].
  7. Wernstedt I, Eriksson AL, Berndtsson A, Hoffstedt J, Skrtic S, Hedner T, et al. A common polymorphism in the interleukin-6 gene promoter is associated with overweight. Int J Obes Relat Metab Disord. 2004;28(10):1272-9. doi: 10.1038/sj.ijo. 0802763. [PubMed: 15303107].
  8. Sopasakis  VR,  Sandqvist  M,  Gustafson  B,  Hammarstedt  A, Schmelz M, Yang X, et al. high local concentrations and effects on differentiation implicate interleukin‐6 as a paracrine regulator. Obes Res. 2004;12(3):454-60. doi: 10.1038/oby. 2004.51. [PubMed: 15044662].
  9. Lieb W, Pavlik R, Erdmann J, Mayer B, Holmer SR, Fischer M, et al. No association of interleukin-6 gene  polymorphism  (− 174 G/C) with myocardial infarction or traditional cardiovascular risk factors. Int J Cardiol. 2004;97(2):205-12. doi: 10.1016/j.ijcard.2003.07.038. [PubMed: 15458685].
  10. Moffett SP, Zmuda JM, Cauley JA, Stone KL, Nevitt MC, Ensrud KE, et al. Association of the G‐174C variant in the interleukin‐6 promoter region with bone loss  and  fracture  risk  in  older women. J Bone Miner Res. 2004;19(10):1612-8. doi: 10.1359/JBMR.040707. [PubMed: 15355555].
  11. 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. doi: 10.1172/ JCI2629. [PubMed: 9769329].
  12. Terry CF, Loukaci V, Green FR. Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J  Biol  Chem.  2000;275(24):18138-44.  doi:  10.1074/jbc.M00 0379200. [PubMed: 10747905].
  13. Acalovschi D, Wiest T, Hartmann M, Farahmi M, Mansmann U, Auffarth GU, et al. Multiple levels of regulation of the interleukin-6 system in stroke. Stroke. 2003;34(8):1864-9. doi: 10.1161/01.STR.0000079815.38626.44. [PubMed: 12843357].
  14. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the  quality of nonrandomized  studies  in meta-analyses. Eur J Epidemiol. 2010;25(9):603-5. doi: 10.1007/s10654-010-9491-z. [PubMed: 20652370].
  15. Hu P, Huang MY, Hu XY, Xie XJ, Xiang MX, Liu XB, et al. Meta- analysis of C242T polymorphism in CYBA genes: risk of acute coronary syndrome is lower in Asians but not in Caucasians. J Zhejiang Univ Sci B. 2015;16(5):370-9. doi: 10.1631/jzus. B1400241. [PubMed: 25990054].
  16. Xiong J, He Z, Zeng X, Zhang Y, Hu Z. Association of vitamin D receptor gene polymorphisms with systemic lupus erythematosus: a meta-analysis. Clin Exp Rheumatol. 2014; 32(2):174-81. [PubMed: 24321519].
  17. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557. doi: 10.1136/bmj.327.7414.557. [PubMed: 12958120].
  18. Gong JY, Sun YH. Association of VEGF gene polymorphisms with diabetic retinopathy: a meta-analysis. PLoS One. 2013; 8(12):e84069. doi: 10.1371/journal.pone.0084069. [PubMed: 24376787].
  19. Berthier MT, Paradis AM, Tchernof A, Bergeron J, Prud'homme D, Després JP, et al. The interleukin 6-174G/C polymorphism is associated with indices of obesity in men. J Hum Genet. 2003;48(1):14-9. doi: 10.1007/s100380300002. [PubMed: 12560873].
  20. Stephens JW, Hurel SJ, Cooper JA, Acharya J, Miller GJ, Humphries SE. A common functional variant in the interleukin-6 gene is associated with increased body mass index in subjects with type 2 diabetes mellitus. Mol Genet Metab. 2004;82(2):180-6. doi: 10.1016/j.ymgme.2004.04.001. [PubMed: 15172007].
  21. Marti  A,  Martinez-González  MA,  Martinez  JA.   Interaction between genes and lifestyle factors on obesity. Proc Nutr Soc. 2008;67(1):1-8. doi: 10.1017/S002966510800596X. [PubMed: 18234126].
  22. Bennermo M, Held C, Stemme S, Ericsson CG, Silveira A, Green F, et al. Genetic predisposition of the interleukin-6 response to inflammation: implications for a variety of major diseases? Clin Chem. 2004;50(11):2136-40. doi: 10.1373/clinchem.2004. 037531. [PubMed: 15364891].
  23. Yudkin   JS,   Kumari   M,   Humphries   SE,   Mohamed-Ali   V. Inflammation, obesity,  stress  and coronary heart  disease:  is interleukin-6 the link? Atherosclerosis. 2000;148(2):209-14. doi: 10.1016/s0021-9150(99)00463-3. [PubMed: 10657556].
  24. Björntorp P. Body fat distribution, insulin resistance, and metabolic diseases. Nutrition. 1997;13(9):795-803. [PubMed: 9290093].
  25. Friedman  JM,  Halaas  JL.  Leptin  and  the  regulation  of  body weight in mammals. Nature. 1998;395(6704):763-70. doi: 10.1038/27376. [PubMed: 9796811].
  26. Cimponeriu D, Serafinceanu C, Apostol P, Toma M, Stavarachi M, Radu I, et al. Potential association of obesity with IL6 G- 174C polymorphism and TTV infections. Central Eur J Biol. 2013;8(7):625-32. doi: 10.2478/s11535-013-0178-1.
  27. Hamid Y, Rose C, Urhammer S, Glümer C, Nolsøe R, Kristiansen O, et al. Variations of the interleukin-6 promoter are associated with features of the metabolic syndrome in Caucasian Danes. Diabetologia. 2005;48(2):251-60. doi: 10.1007/s00125-004- 1623-0. [PubMed: 15645209].
  28. Poitou C, Lacorte JM, Coupaye M, Bertrais S, Bedel JF, Lafon N, et al. Relationship between single nucleotide polymorphisms in leptin, IL6 and adiponectin genes and their circulating product in morbidly obese subjects before and  after  gastric banding surgery. Obes Surg. 2005;15(1):11-23. doi: 10.1381/0960892052993431. [PubMed: 15760495].
  29. Huth C, Illig T, Herder C, Gieger C, Grallert H, Vollmert C, et al. Joint analysis of individual participants’ data from 17 studies on the association of the IL6 variant-174G> C with circulating glucose levels, interleukin-6 levels, and body mass index. Ann Med. 2009;41(2):128-38. doi: 10.1080/07853890802337037 . [PubMed: 18752089].
  30. Yu Z, Han S, Cao X, Zhu C, Wang X, Guo X. Genetic polymorphisms in adipokine genes and the risk of obesity: a systematic review and meta‐analysis. Obesity. 2012;20(2):396- 406. doi: 10.1038/oby.2011.148. [PubMed: 21660081].
  31. Klipstein‐Grobusch  K,  Möhlig  M,  Spranger  J,  Hoffmann  K, Rodrigues  FU,  Sharma  AM,  et  al. Interleukin‐6  g.−  174G> C promoter polymorphism  is  associated  with  obesity  in  the EPIC‐potsdam study. Obesity. 2006;14(1):14-8. doi: 10.1038/oby.2006.3. [PubMed: 16493118].
  32. Bouhaha R, Baroudi T, Ennafaa H, Vaillant E, Abid H, Sassi R, et al. Study of TNFα-308G/A and IL6-174G/C polymorphisms in type 2 diabetes and obesity risk in the Tunisian population. Clin Biochem. 2010;43(6):549-52. doi: 10.1016/j.clinbiochem. 2010.01.008. [PubMed: 20132806].
  33. Underwood PC, Chamarthi B, Williams JS, Sun B, Vaidya A, Raby BA, et al. Replication and meta-analysis of the gene- environment interaction between body mass index and the interleukin-6 promoter polymorphism with higher insulin resistance. Metabolism. 2012;61(5):667-71. doi: 10.1016/j. metabol.2011.09.018. [PubMed: 22075267].