Association of G-174C Polymorphism of the Interleukin-6 Gene Promoter with Obesity in Iranian Population

Authors: Rostami F, Haj Hosseini R, Sharifi K, Daneshpour M, Azizi F, Hedayati M

Abstract:

Expression and secretion of inflammation markers are disturbed in obesity. Interleukin-6 reduces body fat mass. The common G-174C polymorphism in the promoter of IL-6 gene has been reported that effects on transcriptional regulation. The objective was to investigate association of the common polymorphism G-174C with obesity in Iranian population. The present study is cross sectional association study that included 242 individuals (110 men and 132 women). Serum IL-6 levels, C-reactive protein, fasting blood glucose and blood lipids profile were measured .BMI and WHR were calculated. Genotyping is carried out by PCR and RFLP. The frequencies of G and C allele were 64.5% and 35.5%, respectively. The G-174C polymorphism was not associated with BMI and WHR. However in obese individual, fasting blood glucose was significantly higher in carrier of C allele compared with the noncarrier. The IL-6 G-174C polymorphism is not a risk factor for obesity in Iranian population.

Keywords: Interleukin 6, Polymorphism genetic, Obesity.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1071988

References:

[1] Hans Hauner, Symposium on ÔÇÿBiology of obesity-Secretory factors from human adipose tissue and their functional role, Proceedings of the Nutrition Society , pp163-169, 2005.
[2] Lu Qi, Cuilin Zhang, Rob M. van Dam and Frank B. Hu, Interleukin-6 Genetic Variability and Adiposity: Associations in Two Prospective Cohorts and Systematic Review in 26,944 Individuals, Journal of Clinical Endocrinology & Metabolism , 92: 93618-3625, 2007.
[3] I Wernstedt, A-L Eriksson, A Berndtsson1, J Hoffstedt, S Skrtic, T Hedner, LM Hulte'n,O Wiklund, C Ohlsson and J-O Jansson , A common polymorphism in the interleukin-6 genepromoter is associated with overweight, International Journal of Obesity 28, pp 1272-1279, 2004.
[4] Victoria Rotter Sopasakis, Madele'ne Sandqvist,Birgit Gustafson, Ann Hammarstedt, Martin Schmelz, Xiaolin Yang, Per-Anders Jansson, and Ulf Smith , High Local Concentrations and Effectson Differentiation Implicate Interleukin-6 as aParacrine Regulator, Obesity res. 12 :3(454- 461), 2004.
[5] Berthier MT, Paradis AM, Tchernof A, Bergeron J, Prud-homme D, Despres JP, Voh l, MC The interleukin 6-174G/C polymorphism is associated with indices of obesity in men. J Hum Genet 48:14-19, 2003.
[6] Klipstein-Grobusch K, Mohlig M, Spranger J, Hoffmann K, Rodrigues FU, Sharma AM, Klaus S, Pfeiffer AF, Boeing H, Interleukin-6 g.- 174G>C promoter polymorphism is associated with obesity in the EPICPotsdam Study. Obesity (Silver Spring) 14:14-18, 2006.
[7] Lieb W, Pavlik R, Erdmann J, Mayer B, Holmer SR, Fischer M, Baessler A, Hengstenberg C, Loewel H, Doering A, Riegger GA, Schunkert H, No association of interleukin-6 gene polymorphism (-174 G/C) with myocardial infarction or traditional cardiovascular risk factors. Int J Cardiol 97:205-212, 2004.
[8] Moffett SP, Zmuda JM, Cauley JA, Stone KL, Nevitt MC, Ensrud KE, Hillier TA, Hochberg MC, Joslyn G, Morin P, Cummings, 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 19:1612-1618, 2004.
[9] Wallenius V, Wallenius K, Ahre'n B, Rudling M, Carlsten H,Dickson SL, Ohlsson C, Jansson J-O, Interleukin-6-deficient mice develop matureonset obesity. Nat Med 8: 75-79, 2002.
[10] Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S, Woo P. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6levels, and an association with systemic-onset juvenile chronicarthritis. J Clin Invest; 102: 1369-1376, 1998.
[11] Terry CF, Loukaci V, Green FR. Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J BiolChem; 275:18138-18144, 2000.
[12] Acalovschi D, Wiest T, Hartmann M, Farahmi M, Mansmann U,Auffarth GU, Grau AJ, Green FR, Grond-Ginsbach C, SchwaningerM. Multiple levels of regulation of the interleukin-6 system in stroke. Stroke; 34: 1864-1869, 2003.
[13] Kazumi T, Kawaguchi A, Hirano T, Yoshino G. C-reactive protein in young, apparently healthy men: associations with serumleptin, QTc interval, and high-density lipoprotein-cholesterol.Metabolism, 52: 1113- 1116,2003.
[14] Kubaszek A, Pihlajamaki J, Punnonen K, Karhapaa P, Vauhkonen I, Laakso M. The C-174G promoter polymorphism of the IL-6 gene affects energy expenditure and insulin sensitivity. Diabetes,52: 558-561,2003.
[15] Brull DJ, Montgomery HE, Sanders J, Dhamrait S, Luong L, Rumley A, Lowe GD, Humphries SE. Interleukin-6 gene -174g4c and -572g4c promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery. Arterioscler Thromb Vasc Biol; 21: 1458-1463, 2001.
[16] Sothern RB, Roitman-Johnson B, Kanabrocki EL, Yager JG, Roodell MM, Weatherbee JA, Young MR, Nenchausky BM,Scheving LE. Circadian characteristics of circulating interleukin-6 in men. J Allergy Clin Immunol; 95: 1029-1035, 1995.
[17] Farooqi IS, Keogh JM, Kamath S, Jones S, Gibson WT, Trussell R, Jebb SA, Lip GY, O-Rahilly S. Partial leptin deficiency and human adiposity. Nature; 414: 34-35, 2001.
[18] Flier JS. Obesity wars: molecular progress confronts an expandingepidemic. Cell 2004; 116: 337-350.
[19] Wallenius K, Wallenius VW, Sunter D, Dickson SL, Jansson J-O. Intracerebroventricular interleukin-6 treatment decreases bodyfat in rats. Biochem Biophys Res Comm; 293: 560-565, 2002.
[20] Rothwell NJ, Busbridge NJ, Lefeuvre RA, Hardwick AJ, Gauldie J, Hopkins SJ. Interleukin-6 is a centrally acting endogenous pyrogen in the rat. Can J Physiol Pharmacol;69: 1465-1469, 1991.
[21] Stenlof K, Wernstedt I, Fjallman T, Wallenius V, Wallenius K, Jansson JO. Interleukin-6 levels in the central nervous system are negatively correlated with fat mass in overweight/obese subjects. J Clin Endocrinol Metab; 88: 4379-4383, 2003.
[22] Fernandez-Real JM, Ricart W. Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev; 24: 278-301, 2003.
[23] Tsigos C, Papanicolaou DA, Kyrou I, Defensor R, Mitsiadis CS,Chrousos GP. Dose-dependent effects of recombinant human interleukin-6 on glucose regulation. J Clin Endocrinol Metab;82: 4167-4170, 1997.
[24] Stouthard JM, Romijn JA, Van der Poll T, Endert E, Klein S, Bakker PJ, Veenhof CH, Sauerwein HP, Endocrinologic and metabolic effects of interleukin-6 in humans. Am J Physiol; 268: E813-E819, 1995.
[25] Lyngso D, Simonsen L, Bulow J. Metabolic effects of interleukin-6 in human splanchnic and adipose tissue. J Physiol; 543: 379-386, 2002.
[26] Steensberg A, Fischer CP, Sacchetti M, Keller C, Osada T, Schjerling P, van Hall G, Febbraio MA, Pedersen BK. Acute interleukin-6 administration does not impair muscle glucose uptake or whole-body glucose disposal in healthy humans. J Physiol; 548: 631-638, 2003.
[27] Nishimoto N, Yoshizaki K, Maeda K, Kuritani T, Deguchi H, SatoB, Imai N, Suemura M, Kakehi T, Takagi N, Kishimoto T. Toxicity, pharmacokinetics, and dose-finding study of repetitive treatment with the humanized anti-interleukin 6 receptor antibody MRA in rheumatoid arthritis. Phase I/II clinical study. J Rheumatol; 30: 1426-1435, 2003.