Excessive fat accumulation is associated with the TNFα-308 G/A promoter polymorphism in women but not in men
Excessive fat accumulation is associated with the TNFα-308 G/A promoter polymorphism in women but not in men
复制标题
DOI：
10.1007/s001250050015
复制
发表时间：
2000-01-01
期刊：
影响因子：
8.2
通讯作者：
Arner, P
中科院分区：
文献类型：
--
作者：
Hoffstedt, J;Eriksson, P;Arner, P
目标/假设。肿瘤坏死因子α（TNFα）是导致肥胖的候选基因，而肥胖又是糖尿病的主要危险因素。我们研究的目的是调查 TNF α 基因启动子区先前已知的 NcoI 敏感多态性 (-308 G/A) 是否与体重相关。对 239 名男性和 342 名女性非糖尿病受试者进行了基因分型，这些受试者的体重指数 (BMI) 存在显着差异。结果。我们发现了三种基因型； AA (n = 13)、AG (n = 158) 和 GG (n = 410)。当根据性别对材料进行分类时，等位基因特异性表型差异仅限于女性。携带AA基因型的女性受试者明显比AG和GG携带者肥胖（平均BMI分别为41.4 vs 32.3和31.7 kg/m(2)，p = 0.02），与AG/GG携带者相比，女性AA携带者的体脂含量增加了三分之一（p = 0.02）。我们发现基因型之间在腰臀比、血压或代谢变量方面没有差异。在肥胖女性受试者（BMI > 27 kg/m(2)）中，我们还发现AA携带者（n = 7）的BMI和体脂含量也高于AG/GG携带者。结论/解释。 TNFα基因启动子区-308位的AA变体可能是女性脂肪过度积累的重要遗传因素。
Aims/hypothesis. Tumour necrosis factor alpha (TNF alpha) is a candidate gene for the development of obesity, which in turn is a major risk factor for diabetes mellitus. The aim of our study was to investigate whether a previously known NcoI-sensitive polymorphism (-308 G/A) in the promoter region of the TNF alpha gene was related to body weight.Methods. Genotyping was done in 239 male and 342 female non-diabetic subjects with a marked variation in body mass index (BMI).Results. We found three genotypes; AA (n = 13), AG (n = 158) and GG (n = 410). When the material was divided according to sex, allele specific phenotypic differences were confined to women. The female subjects carrying the AA genotype were markedly more obese than both the AG and GG carriers (mean BMI = 41.4 vs 32.3 and 31.7 kg/m(2), respectively, p = 0.02), The body fat content of female AA carriers was increased by one-third compared with AG/GG carriers (p = 0.02). We found no differences between genotypes with respect to waist-to-hip ratio, blood pressure or metabolic variables. Among obese female subjects (BMI > 27 kg/m(2)), we also found that the BMI and body fat content of AA carriers (n = 7) were also higher than for AG/GG carriers.Conclusion/interpretation. The AA-variant at position -308 in the promoter region of the TNF alpha gene could be an important genetic factor behind excessive fat accumulation in women.