ENPP1 variants and haplotypes predispose to early onset obesity and impaired glucose and insulin metabolism in German obese children
ENPP1 variants and haplotypes predispose to early onset obesity and impaired glucose and insulin metabolism in German obese children
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DOI：
10.1210/jc.2006-0540
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发表时间：
2006-12-01
影响因子：
5.8
通讯作者：
Kovacs, Peter
中科院分区：
文献类型：
--
作者：
Boettcher, Yvonne;Koerner, Antje;Kovacs, Peter
内容：ENPP 1（核苷酸焦磷酸酶/磷酸二酯酶-1）编码一种膜结合糖蛋白，可抑制胰岛素受体酪氨酸激酶活性，导致胰岛素敏感性降低。因此，该基因的变异可能与肥胖和胰岛素抵抗有关。目的：因此，在这项研究中，我们旨在探讨ENPP 1基因变异在肥胖和相关性状中的作用，在高加索儿童的代表性人群和肥胖儿童的队列中，详细的代谢特征包括口服葡萄糖耐量试验。设计：我们对712名学龄儿童的K121 Q、IVS 20 delT-11和A/G+1044 TGA ENPP 1基因变异进行了基因分型，以进行关联分析（346名男孩和366名女孩;平均年龄12 ± 3岁;平均体重指数-SD评分0.09 +/-0.04）和来自莱比锡的205名肥胖儿童和来自德国达特尔恩的195名肥胖儿童的独立队列中。我们发现携带121 Q变异的莱比锡儿童肥胖风险显著增加（校正比值比，1.82; 95%可信区间，1.30-2.56; P = 0.0005）或[Q-delT-G]单倍型[1.75（1.17-2.62），P = 0.006]。这在另一个来自莱比锡的独立肥胖/超重队列以及来自Datteln的肥胖儿童中得到了复制。此外，来自莱比锡的[Q-delT-G]单倍型肥胖儿童的特征是糖代谢受损，而[K-delT-G]和[K-insT-A]单倍型与胰岛素敏感性和糖代谢改善显著相关（校正年龄、性别和体重指数后，所有P均< 0.05）。总之，我们的研究表明K121 Q多态性或衍生ENPP 1单倍型在儿童肥胖易感性增加和葡萄糖和胰岛素代谢早期受损中的潜在作用。
Context: ENPP1 (nucleotide pyrophosphatase/phosphodiesterase-1) encodes a membrane-bound glycoprotein that inhibits the insulin-receptor tyrosine kinase activity, resulting in reduced insulin sensitivity. Hence, variants in this gene may be related to obesity and insulin resistance.Objective: Therefore, in this study, we aimed to explore the role of ENPP1 genetic variants in obesity and related traits in a representative population of Caucasian children and in cohorts of obese children with detailed metabolic characteristics including oral glucose tolerance test.Design: We genotyped the K121Q, IVS20delT-11, and A/G+1044TGA ENPP1 genetic variants for association analyses in 712 schoolchildren (346 boys and 366 girls; mean age 12 +/- 3 yr; mean body mass index-SD score 0.09 +/- 0.04) and in independent cohorts of 205 obese children from Leipzig and 195 obese children from Datteln, Germany.Results: We identified a significantly increased risk of obesity in Leipzig children carrying the 121Q variant (adjusted odds ratio, 1.82; 95% confidence interval, 1.30-2.56; P = 0.0005) or the [Q-delT-G] haplotype [1.75 (1.17-2.62), P = 0.006] as compared with a lean control group. This was replicated in another independent obesity/ overweight cohort from Leipzig as well as obese children from Datteln. In addition, obese children from Leipzig with the [Q-delT-G] haplotype were characterized by impaired glucose metabolism, whereas the [K-delT-G] and [K-insT-A] haplotypes were significantly associated with improved insulin sensitivity and glucose metabolism (all P < 0.05 after adjusting for age, gender, and body mass index).Conclusions: In conclusion, our study suggests a potential role of the K121Q polymorphism or derived ENPP1 haplotypes in increased susceptibility to obesity and early impairment of glucose and insulin metabolism in children.