Structural Analysis Of Candidate Genes For Type 2 Diabetes and Obesity

一个基因被认为是皮马印第安人2型糖尿病的候选基因，如果1）它在与2型糖尿病/肥胖症相关的途径中具有已知的生理功能，或2）它与另一个人群或动物模型中的糖尿病/肥胖症相关。在过去的一年中，我们直接测序和基因分型所有检测到的变异在20多个生理候选基因与BMI或糖尿病的关联。我们最近发现Sim 1是皮马印第安人肥胖的第一个主要易感基因，该基因的变异约占16磅。我们还与Mark McCarthy博士和Andrew Hattersley博士合作研究FTO基因，该基因最近被报道与白人的BMI高度相关。我们的研究小组在非高加索人群中首次获得了该基因的数据，该基因在皮马印第安人中显示出与BMI相似的关联，并且还通过显示该基因对确定脂肪细胞大小具有特定影响来进一步促进了最初的发现-这一观察结果正在敲除小鼠中进行。相比之下，我们已经表明，TCF 7 L2的变化，强烈预测2型糖尿病在多个种族群体，没有决定2型糖尿病在皮马印第安人的作用。

A gene is considered a candidate gene for type 2 diabetes in Pima Indians if 1) it has a known physiological function in a pathway relevant to type 2 diabetes/obesity or 2) it is associated with diabetes/obesity in another human population or in an animal model. In the past year we have directly sequenced and genotyped all detected variants in more than 20 physiologic candidate genes for associations with BMI or diabetes. We have recently found Sim1 to be the first major susceptibility gene for obesity in the Pima Indians, where variation in this gene accounts for approximately 16 lbs. We have also been collaborating with Dr Mark McCarthy and Dr Andrew Hattersley on the FTO gene, which has recently been reported to be highly associated with BMI in Caucasians. Our group has the first data on this gene in a non-Caucasian population, where the gene shows a similar association with BMI in Pima Indians, and has also furthered the initial finding by showing that this gene has a specific effect on determining fat cell size- an observation that is being followed up on in knockout mice. In contrast, we have shown that variation in TCF7L2, which strongly predicts type 2 diabetes in multiple ethnic groups, has no role in determining type 2 diabetes in Pima Indians.