A number of candidate genes have been in implicated in the pathogenesis of obesity in humans. Tumor necrosis factor-alpha (TNFalpha) is expressed primarily in adipocytes, and elevated levels of this cytokine have been linked to obesity and insulin resistance. Recently, the A allele of a polymorphism at position -308 in the promoter region of TNFalpha (G-308A) has been shown to increase transcription of the gene in adipocytes. We therefore designed this study to test whether obese and non-obese subjects differ in terms of TNFalpha genotype distribution. We also investigated whether the genotypes affect anthropometric parameters, such as body mass index (BMI). The study included 153 obese healthy women and 82 non-obese women. Total fat mass and percent body fat were determined by dual-energy X-ray absorptiometry. Genomic DNA was extracted and used for NcoI restriction fragment length polymorphism-based genotyping of TNFalpha. No differences were observed in allele and genotype frequencies between obese and non-obese women, and no association of TNFalpha polymorphism with BMI was observed for genotype in the obese women. In addition, age, percent body fat, BMI, and cholesterol levels did not vary with TNFalpha genotype. However, waist-to-hip ratio (WHR) was significantly lower in subjects with TNFalpha GA or AA genotypes (0.94 +/- 0.07 vs. 0.92 +/- 0.03, P < 0.005). These results indicate that polymorphism at position -308 of the TNFalpha promoter is not a significant factor for BMI, but affects WHR in obese healthy Korean women.
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