Um Jae-Young, Kang Byung-Ku, Lee Si-Hyeong, Shin Jo-Young, Hong Seung-Heon, Kim Hyung-Min
Department of Pharmacology, College of Oriental Medicine, Kyung Hee University, Seoul 130-701, Korea.
Mol Cells. 2004 Dec 31;18(3):340-5.
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.
许多候选基因被认为与人类肥胖的发病机制有关。肿瘤坏死因子-α（TNFα）主要在脂肪细胞中表达，这种细胞因子水平的升高与肥胖和胰岛素抵抗有关。最近，TNFα启动子区域-308位多态性的A等位基因（G-308A）已被证明可增加该基因在脂肪细胞中的转录。因此，我们设计了本研究，以测试肥胖和非肥胖受试者在TNFα基因型分布方面是否存在差异。我们还研究了这些基因型是否会影响人体测量参数，如体重指数（BMI）。该研究包括153名肥胖健康女性和82名非肥胖女性。通过双能X线吸收法测定总脂肪量和体脂百分比。提取基因组DNA并用于基于NcoI限制性片段长度多态性的TNFα基因分型。在肥胖和非肥胖女性之间未观察到等位基因和基因型频率的差异，在肥胖女性中也未观察到TNFα多态性与BMI的关联。此外，年龄、体脂百分比、BMI和胆固醇水平并不随TNFα基因型而变化。然而，TNFα基因型为GA或AA的受试者的腰臀比（WHR）显著较低（0.94±0.07对0.92±0.03，P<0.005）。这些结果表明，TNFα启动子-308位的多态性不是BMI的重要影响因素，但会影响肥胖健康韩国女性的WHR。
