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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
Department of Biotechnology, Panjab University, India.
Department of Biotechnology, Panjab University, India.
Department of Cardiology, PGIMER, Chandigarh 160012, India.
Department of Cardiology, PGIMER, Chandigarh 160012, India.
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2012 (English)In: Molecular and Cellular Biochemistry, ISSN 0300-8177, E-ISSN 1573-4919, Vol. 360, no 1-2, 1-7 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Springer, 2012. Vol. 360, no 1-2, 1-7 p.
National Category
Cancer and Oncology
Research subject
Medical sciences
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URN: urn:nbn:se:his:diva-9003DOI: 10.1007/s11010-011-0917-zISI: 000297722800001PubMedID: 22081334ScopusID: 2-s2.0-83555176087OAI: oai:DiVA.org:his-9003DiVA: diva2:712825
Available from: 2014-04-16 Created: 2014-04-16 Last updated: 2016-10-27Bibliographically approved

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Singh, Neha
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