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

11-beta hydroxysteroid dehydrogenase (11-beta HSD1), tumor necrosis factor-alpha (TNF-alpha) and their role in obesity, regional adiposity and insulin resistance has been sparsely evaluated. We determined the polymorphic status of 11-beta HSD1 4478T > G and TNF-alpha-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-beta HSD1 and TNF-alpha were analyzed with obesity [BMI a parts per thousand yen 25 kg/m(2), 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-beta HSD1 were 89.57 and 10.43 respectively. Homozygosity for 11-beta HSD1 4478G/G was absent with no association with parameters of obesity and insulin resistance. Frequencies (%) of TNF-alpha [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-alpha-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-alpha genotype showed higher subscapular skinfold predisposing them to truncal subcutaneous adiposity (p = 0.02). Our findings of association of TNF-alpha-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-alpha-308G > A in this population.