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

• Published in: Molecular biology reports Vol. 40; no. 11; pp. 6261 - 6270
• Main Authors: Sharma, Mukti, Vikram, Naval Kishore, Misra, Anoop, Bhatt, SuryaPrakash, Tarique, Mohammed, Parray, Hilal Ahmad, Pandey, Ravindra Mohan, Luthra, Kalpana
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.11.2013
• Subjects: 11-beta-Hydroxysteroid Dehydrogenases - genetics; adiposity; Adult; Alleles; Animal Anatomy; Animal Biochemistry; Asian Indians; Biomedical and Life Sciences; body mass index; cholesterol; Codon; Cross-Sectional Studies; dual-energy X-ray absorptiometry; Female; females; Gene Frequency; Genotype; Histology; homozygosity; Humans; India; insulin resistance; Insulin Resistance - genetics; Life Sciences; Lipid Metabolism; magnetic resonance imaging; Male; males; Middle Aged; Morphology; necrosis; obesity; Obesity - genetics; Obesity - metabolism; Odds Ratio; Phenotype; polymerase chain reaction; Polymorphism, Single Nucleotide; restriction fragment length polymorphism; Sex Factors; triacylglycerols; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - genetics; very low density lipoprotein; waist-to-hip ratio; Young Adult; India; Obesity; Subscapular skin fold; Body fat; Polymorphisms; -; Asian Indians
• ISSN: 0301-4851; 1573-4978; 1573-4978
• DOI: 10.1007/s11033-013-2738-5

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.