Tumor necrosis factor-α-308 G/A polymorphism in obese Caucasians
Tumor necrosis factor-α-308 G/A polymorphism in obese Caucasians
复制标题
DOI：
10.1038/sj.ijo.0801576
复制
发表时间：
2001-04-01
影响因子：
4.9
通讯作者：
Sharma, AM
中科院分区：
文献类型：
--
作者：
Brand, E;Schorr, U;Sharma, AM
目的：肿瘤坏死因子-α（TNF-α）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，据报道，TNF-α基因（G-308 A）5-侧翼区多态性的A等位基因在肥胖受试者中比在瘦受试者中更常见，并且还与脂肪组织中该细胞因子的表达增加相关，并影响脂肪量和胰岛素抵抗。因此，我们研究了这种变异和肥胖之间的关系，在德国高加索population.SUBJECTS和方法：我们基因分型176指数主体的框架内招募的贝格（柏林Ernahrung Geschwister）-研究TNF-α-G-308 A多态性。受试者的特点是体重，身高，腰围和臀围，身体质量指数（BMI），身体成分，葡萄糖耐量，瘦素和血管紧张素原levels.Results：-308 A等位基因的频率（0.18）是相似的，以前的报道和基因型分布在哈代-温伯格平衡（CC，n = 118; CA，n = 53; AA，n = 5）。不同BMI四分位数的等位基因频率差异有统计学意义（Ⅰ）< 27.3 kg/m（2）; Ⅱ）27.3 - 31.9 kg/m（2）; Ⅲ）31.9 - 36.5 kg/m（2）; IV，> 36.5 kg/m2，每个四分位数n = 44），-308 A等位基因携带者的BMI高于G等位基因携带者（P = 0.013）。尽管以前的小型研究将胰岛素抵抗与G-308 A多态性联系起来，但我们在口服葡萄糖耐量试验（OGTT）和多态性期间没有发现葡萄糖和胰岛素反应之间的关系。此外，没有血浆参数相关的多态性。结论：我们的研究结果支持这一假设，即G-308 A多态性的TNF-α？基因与BMI有关。因此，G-308 A多态性可能是高加索人肥胖易感性增加的遗传标记。
OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) 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 in the 5-flanking region of the TNF-alpha gene (G-308A) has been reported to be more frequent in obese than in lean subjects and has also been associated with increased expression of this cytokine in fat tissue and influences fat mass and insulin resistance. We, therefore, examined the relationship between this variant and obesity in a German Caucasian population.SUBJECTS AND METHODS: We genotyped 176 index subjects recruited within the framework of the BErG (Berlin Ernahrung Geschwister)- Study for the TNF-alpha -G-308A polymorphism. Subjects were characterized for weight, height, waist and hip circumference, body mass index (BMI), body composition, glucose tolerance, leptin and angiotensinogen levels.RESULTS: The frequency of the -308A allele (0.18) was similar to that reported previously and genotype distribution was in Hardy -Weinberg equilibrium (CC, n = 118; CA, n = 53; AA, n = 5). There was a significant difference in allele frequencies of the polymorphism by BMI quartiles (I, < 27.3 kg/m(2); II, 27.3 - 31.9 kg/m(2); III, 31.9 - 36.5 kg/m(2); IV, > 36.5 kg/m(2), in each quartile n = 44) with -308A allele carriers having a higher BMI than G allele carriers (P = 0.013). Despite previous smaller studies that have related insulin resistance to the G-308A polymorphism, we found no relationship between glucose and insulin response during an oral glucose tolerance test (OGTT) and the polymorphism. Furthermore, none of the plasma parameters were related to the polymorphism.CONCLUSION: Our findings support the hypothesis that the G-308A polymophism of the TNF-alpha? gene is associated with BMI. The G-308A polymorphism may, therefore, represent a genetic marker for increased susceptibility for obesity in Caucasians.