title: Risk of obesity and type 2 diabetes with tumor necrosis factor-α 308G/A gene polymorphism in metabolic syndrome and coronary artery disease subjects.
abstract: Tumor Necrosis Factor-alpha (TNF-α) has been implicated in the pathogenesis of insulin resistance and obesity. The increased expression of TNF-α in adipose tissue is known to induce insulin resistance, and a polymorphism at position -308 in the promoter region of TNF-α gene may lead to its increased transcription in adipocytes. The objective of this work was to determine the role of TNFα-308G/A gene polymorphism in metabolic syndrome (MetS) and coronary artery disease (CAD) with obesity and type 2 diabetes mellitus (T2DM). A total of 250 MetS and 224 CAD patients and 214 controls were studied. TNFα-308G/A polymorphism was detected from the whole blood genomic DNA using PCR-amplification refractory mutation system. The 2 × 2 contingency tables and multiple regression analysis were used for determining the association of genotypes with obesity and type 2 diabetes mellitus (T2DM) in MetS and CAD subjects. In CAD subjects with T2DM, the AG genotypes showed a very strong association (P < 0.0001; OR 0.194, 95%CI 0.103-0.365). In CAD subjects with obesity, the AA (P = 0.049; OR 2.449) and AG genotypes showed a strong association (P < 0.0001; OR 0.206). In both males and females, AG genotype and G allele (P < 0.0001) showed a strong association with T2DM. In MetS subjects with T2DM, there was a strong association with AG (P = 0.002; OR 4.483) as well as AA+AG genotypes (P = 0.002; OR 4.255). The AA and AG genotype (P = 0.001; OR 5.497) in males showed a strong 4.6- and 5.4-fold risks, respectively, with obesity. In females, only AG genotype showed a strong 4.5-fold risk with obesity (P = 0.001). In MetS subjects with obesity, the AA genotype (P = 0.043; OR 3.352) as well as AG showed a very strong association (P = 0.001; OR 5.011). The AG genotypes showed a high 3.5-fold risk with T2DM in females (P = 0.011). In CAD subjects, AG genotype showed a protective effect in both obese males and females (P < 0.0001). Heterozygous TNFα-308G/A gene variant may be an important risk factor for MetS with T2DM and obesity in both males and females, but may have a protective role in CAD subjects with obesity and T2DM. A allele may be an important risk factor for MetS and CAD with obesity as well as CAD subjects with T2DM.
authors.affiliation: Department of Biotechnology, Panjab University, Chandigarh, India.
authors.forename: Ranbir Chander
authors.initials: RC
authors.lastname: Sobti
authors.forename: Rupinder
authors.initials: R
authors.lastname: Kler
authors.forename: Yash Paul
authors.initials: YP
authors.lastname: Sharma
authors.forename: Kewal Krishan
authors.initials: KK
authors.lastname: Talwar
authors.forename: Neha
authors.initials: N
authors.lastname: Singh
mesh_terms: D000328:Adult; D000483:Alleles; D003324:Coronary Artery Disease / Q000150:complications / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000209:etiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012044:Regression Analysis; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D012737:Sex Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D014409:Tumor Necrosis Factor-alpha
references.citation: Proc Soc Exp Biol Med. 2000 Feb;223(2):128-35
references.pmid: 10654615
references.citation: Mol Biol Rep. 2011 Nov;38(8):4971-7
references.pmid: 21153921
references.citation: Heart Lung Circ. 2008 Feb;17(1):14-8
references.pmid: 17581788
references.citation: Obes Res. 2002 May;10(5):401-7
references.pmid: 12006640
references.citation: Arterioscler Thromb Vasc Biol. 1996 Feb;16(2):281-8
references.pmid: 8620344
references.citation: JAMA. 2001 May 16;285(19):2486-97
references.pmid: 11368702
references.citation: J Clin Invest. 1994 Oct;94(4):1543-9
references.pmid: 7523453
references.citation: Genes Immun. 2001 Apr;2(2):61-70
references.pmid: 11393658
references.citation: Clin Chem. 1999 Aug;45(8 Pt 2):1339-45
references.pmid: 10430816
references.citation: J Biol Chem. 1993 Dec 15;268(35):26055-8
references.pmid: 8253716
references.citation: Science. 1996 Feb 2;271(5249):665-8
references.pmid: 8571133
references.citation: Nature. 1997 Oct 9;389(6651):610-4
references.pmid: 9335502
references.citation: BMC Med Genet. 2001;2:10
references.pmid: 11570978
references.citation: J Investig Med. 2000 Jul;48(4):236-44
references.pmid: 10916281
references.citation: Obes Res. 2005 Dec;13(12):2122-31
references.pmid: 16421346
references.citation: Neuropsychologia. 2011 Jan;49(2):196-202
references.pmid: 21130787
references.citation: J Nutr. 2010 May;140(5):901-7
references.pmid: 20335630
references.citation: Clin Chem Lab Med. 2009;47(10):1247-51
references.pmid: 19803813
references.citation: Expert Opin Ther Targets. 2001 Jun;5(3):297-301
references.pmid: 12540266
references.citation: Cancer Res. 2002 Jun 15;62(12):3369-72
references.pmid: 12067976
references.citation: Trends Endocrinol Metab. 2000 Aug;11(6):212-7
references.pmid: 10878750