Association of variants in gastric inhibitory polypeptide receptor gene with impaired glucose homeostasis in obese children and adolescents from Berlin
Association of variants in gastric inhibitory polypeptide receptor gene with impaired glucose homeostasis in obese children and adolescents from Berlin
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DOI：
10.1530/eje-10-0444
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发表时间：
2010-08-01
影响因子：
5.8
通讯作者：
Biebermann, Heike
中科院分区：
文献类型：
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作者：
Sauber, Jeannine;Grothe, Jessica;Biebermann, Heike
目的：在过去的20年里，肥胖已成为一个主要的健康问题，由于相关的疾病，如2型糖尿病。胃抑制多肽受体（GIPR）调节体重和葡萄糖稳态，因此，代表了一个有趣的候选基因肥胖和合并症受损的葡萄糖稳态。最近，GIPR变异被发现与人类胰岛素反应受损有关，在本研究中，我们筛选了GIPR基因的突变，并检查了三个单核苷酸多态性之间的关联（SNPs; rs 8111428、rs 2302382、rs 1800437）与儿童肥胖以及葡萄糖稳态受损相关。通过直接测序筛选GIPR的编码区的突变。我们在2280名健康正常体重（1696）和肥胖（584）儿童和青少年中对三种已知的SNPs进行了基因分型。使用SNaPshot方案、iplex和基质辅助激光解吸电离飞行时间光谱技术进行基因分型。肥胖定义为身体质量指数SDS高于2;稳态模型评估calculated.Results：没有证据表明SNPs和肥胖表型之间的关联。SNP rs 1800437的次要等位基因C与胰岛素抵抗值升高的稳态模型之间存在显著关联（P=0.001）。结论：GIPR序列变异与儿童肥胖无关。这项研究指出了rs 1800437在葡萄糖稳态中的潜在作用。需要进一步的研究来证实这些结果。
Objective: In the past 20 years, obesity has become a major health problem due to associated diseases like type 2 diabetes mellitus. The gastric inhibitory polypeptide receptor (GIPR) modulates body weight and glucose homeostasis and, therefore, represents an interesting candidate gene for obesity and the comorbidity impaired glucose homeostasis. Recently, a GIPR variation was found to be associated with impaired insulin response in humans.In this study, we screened the GIPR gene for mutations and examined the association between three single-nucleotide polymorphisms (SNPs; rs8111428, rs2302382, rs1800437) and childhood obesity, as well as impaired glucose homeostasis.Methods: The coding region of the GIPR was screened for mutations by direct sequencing. We genotyped three known SNPs in 2280 healthy normal weight (1696) and obese (584) children and adolescents. Genotyping was performed using the SNaPshot protocol, the iplex, and matrix-assisted laser desorption ionization time-of-flight spectrometry technique. Obesity was defined by a body mass index SDS above 2; homeostatic model assessment was calculated.Results: No evidence for an association was found between the SNPs and the obesity phenotype. Significant association was found between the minor allele C of the SNP rs1800437 and elevated homeostasis model of insulin resistance values (P=0.001). No further sequence variations in the GIPR were found to be associated with childhood obesity.Conclusion: Variations of the GIPR sequence are not associated with childhood obesity. This study points to a potential role for rs1800437 in glucose homeostasis. Further studies are necessary to confirm these results.