TCF7L2 gene polymorphisms confer an increased risk for early impairment of glucose metabolism and increased height in obese children
TCF7L2 gene polymorphisms confer an increased risk for early impairment of glucose metabolism and increased height in obese children
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DOI：
10.1210/jc.2006-2514
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发表时间：
2007-05-01
影响因子：
5.8
通讯作者：
Kovacs, Peter
中科院分区：
文献类型：
--
作者：
Koerner, Antje;Berndt, Janin;Kovacs, Peter
背景：转录因子7样2（TCF 7 L2）基因变异与成人2型糖尿病风险增加相关。为了评估这五种已报道的风险变异是否会增加儿童肥胖和早期糖代谢受损的风险，我们对1029名白人儿童的代表性队列和283名肥胖儿童的独立队列进行了TCF 7 L2基因的基因分型。应用病例对照设计，我们观察到肥胖儿童（n=283）中rs 11196205和rs7895340风险等位基因的患病率显著低于瘦儿童（n=672）（0.40 vs. 0.45; P=0.02）。然而，在正常代表性队列（n=1029）或肥胖队列中，这些基因型与肥胖的数量性状之间没有统计学显著关系。肥胖儿童明显比瘦儿童高。这种身高的增加与TCF 7 L2基因的风险变体独立相关，而在正常代表性队列中，次要等位基因携带者的身高似乎降低。在肥胖队列中，三个风险等位基因（rs7901695，rs7903146和rs 1225572）与较高的空腹和120分钟血糖水平显著相关，与性别，年龄，青春期阶段和体重指数无关。空腹和峰值胰岛素水平和HOMA-IR出现了类似的趋势，但没有统计学意义。结论：我们的数据首次表明，TCF 7 L2基因变异赋予肥胖儿童早期糖代谢受损的风险增加，这与成人研究确定TCF 7 L2作为一个主要的糖尿病易感基因是一致的。
Context: Variants in the transcription factor 7-like2 (TCF7L2) gene have been associated with an increased risk for type 2 diabetes in adults. To evaluate whether the five reported risk variants confer a higher risk for obesity and early impairment of glucose metabolism in children, we genotyped these risk variants of the TCF7L2 gene in a representative cohort of 1029 Caucasian children and an independent cohort of 283 obese children.Results: Applying a case control design, we observed a significantly lower prevalence of the rs11196205 and rs7895340 risk alleles in the obese (n=283) compared with lean (n=672) children (0.40 vs. 0.45; P=0.02). There was, however, no statistically significant relationship between these genotypes and quantitative traits of obesity in either a normal representative cohort (n=1029) or an obesity cohort. Obese children were significantly taller than lean children. This increase in height was independently associated with risk variants of the TCF7L2 gene, whereas in the normal representative cohort height appeared to be decreased in carriers of the minor alleles. In the obese cohort, three risk alleles (rs7901695, rs7903146, and rs1225572) were significantly associated with higher fasting and 120-min blood glucose levels independent of sex, age, pubertal stage, and body mass index. Fasting and peak insulin levels and HOMA-IR appeared with a similar tendency but were not statistically significant.Conclusions: Our data indicate for the first time that TCF7L2 gene variants confer an increased risk for early impairment of glucose metabolism in obese children, which is consistent with adult studies identifying TCF7L2 as a major diabetes susceptibility gene.