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Assessment of 11-β hydroxysteroid dehydrogenase (11-βHSD1) 4478T>G and tumor necrosis factor-α (TNF-α)-308G>A polymorphisms with obesity and insulin resistance in Asian Indians in North India

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Abstract

11-β hydroxysteroid dehydrogenase (11-βHSD1), tumor necrosis factor-α (TNF-α) and their role in obesity, regional adiposity and insulin resistance has been sparsely evaluated. We determined the polymorphic status of 11-βHSD1 4478T>G and TNF-α-308G>A in Asian Indians in north India. In this cross-sectional study (n = 498; 258 males, 240 females), association of genotypes (PCR–RFLP) of 11-βHSD1 and TNF-α were analyzed with obesity [BMI ≥ 25 kg/m2, percentage body fat (%BF by DEXA); subcutaneous and intra-abdominal fat area (L2–3 level by single slice MRI) in a sub sample] and insulin resistance. 46 percent subjects had generalized obesity, 55 % abdominal obesity and 23.8 % were insulin resistant. Frequencies (%) of [T/T] and [T/G] genotypes of 11-βHSD1 were 89.57 and 10.43 respectively. Homozygosity for 11-βHSD1 4478G/G was absent with no association with parameters of obesity and insulin resistance. Frequencies (%) of TNF-α [G] and [A] alleles were 88 and 12 respectively. Higher frequency of variant -308[A/A] was observed in females versus males (p = 0.01). Females with at least one single A allele of TNF-α-308G>A had significantly high %BF and total skinfold, whereas higher values of waist hip ratio, total cholesterol, triglycerides and VLDL were observed in males. Subjects with even a single A allele in TNF-α genotype showed higher subscapular skinfold predisposing them to truncal subcutaneous adiposity (p = 0.02). Our findings of association of TNF-α-308G>A variant in females with obesity indices suggests a gender-specific role of this polymorphism in obesity. High truncal subcutaneous adiposity is associated with A allele of TNF-α-308G>A in this population.

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Acknowledgments

We are thankful to all the subjects who participated in this study. This work was supported by a grant from the Department of Biotechnology (DBT- N881), New Delhi, India.

Conflicts of interest

The authors declare that they have no conflicts of interest concerning this article.

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Authors and Affiliations

  1. Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), New Delhi, India

    Mukti Sharma, Mohammed Tarique, Hilal Ahmad Parray & Kalpana Luthra

  2. Department of Medicine, All India Institute of Medical Sciences, New Delhi, India

    Naval Kishore Vikram & SuryaPrakash Bhatt

  3. National Diabetes, Obesity and Cholesterol Foundation (N-DOC), Diabetes and Metabolic Diseases, Diabetes Foundation India (DFI), New Delhi, India

    Anoop Misra

  4. Department of Biostatistics, All India Institute of Medical Sciences (AIIMS), New Delhi, India

    Ravindra Mohan Pandey

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  1. Mukti Sharma
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Sharma, M., Vikram, N.K., Misra, A. et al. Assessment of 11-β hydroxysteroid dehydrogenase (11-βHSD1) 4478T>G and tumor necrosis factor-α (TNF-α)-308G>A polymorphisms with obesity and insulin resistance in Asian Indians in North India. Mol Biol Rep 40, 6261–6270 (2013). https://doi.org/10.1007/s11033-013-2738-5

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