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.

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/m(2), percentage body fat (%BF by DEXA); subcutaneous and intra-abdominal fat area (L(2-3) 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.

• Authors: Mukti Sharma, Naval Kishore Vikram, Anoop Misra, SuryaPrakash Bhatt, Mohammed Tarique, Hilal Ahmad Parray, Ravindra Mohan Pandey, Kalpana Luthra
• Journal: Molecular biology reports (Mol Biol Rep) Vol. 40 Issue 11 Pg. 6261-70 (Nov 2013) ISSN: 1573-4978 [Electronic] Netherlands
• PMID: 24078163 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Codon
• Tumor Necrosis Factor-alpha
• 11-beta-Hydroxysteroid Dehydrogenases

Topics

• 11-beta-Hydroxysteroid Dehydrogenases (genetics)
• Adult
• Alleles
• Codon
• Cross-Sectional Studies
• Female
• Gene Frequency
• Genotype
• Humans
• India
• Insulin Resistance (genetics)
• Lipid Metabolism
• Male
• Middle Aged
• Obesity (genetics, metabolism)
• Odds Ratio
• Phenotype
• Polymorphism, Single Nucleotide
• Sex Factors
• Tumor Necrosis Factor-alpha (genetics)
• Young Adult