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Risk of obesity and type 2 diabetes with tumor necrosis factor-α 308G/A gene polymorphism in metabolic syndrome and coronary artery disease subjects

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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.

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Authors and Affiliations

  1. Department of Biotechnology, Panjab University, Sector-14, Chandigarh, 160014, India

    Ranbir Chander Sobti, Rupinder Kler & Neha Singh

  2. Department of Cardiology, PGIMER, Chandigarh, 160012, India

    Yash Paul Sharma & Kewal Krishan Talwar

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  1. Ranbir Chander Sobti
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  2. Rupinder Kler
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  3. Yash Paul Sharma
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  4. Kewal Krishan Talwar
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  5. Neha Singh
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Correspondence to Rupinder Kler.

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Sobti, R.C., Kler, R., Sharma, Y.P. et al. Risk of obesity and type 2 diabetes with tumor necrosis factor-α 308G/A gene polymorphism in metabolic syndrome and coronary artery disease subjects. Mol Cell Biochem 360, 1–7 (2012). https://doi.org/10.1007/s11010-011-0917-z

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  • DOI: https://doi.org/10.1007/s11010-011-0917-z

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