Structural Analysis of Candidate Genes for type 2 Diabetes

基因被认为是2型的候选基因 Pimas的糖尿病，如果1）它与糖尿病表型相关， 另一个群体或2）它具有生理相关功能 并位于与糖尿病相关的染色体区域。 迄今已分析的候选基因包括 与其他种群中的Mody相关的基因。我们 鉴定了HNF 1？中的几种多态性，HNF1b和HNF3b 基因，但没有一个与皮马斯的早发性糖尿病有关。 然而，HNFlb中的一种多态性预测了HNFlb的非保守性。 蛋白质关键区域内的氨基酸取代， 因此，正在进一步研究功能变异性， 转染细胞系。我们还分析了候选基因， 1号染色体上与糖尿病有关的区域。无多态性 与糖尿病相关的丙酮酸激酶或 类维生素A X受体γ基因我们发现了一个 多态性的启动子和4个多态性的3？ ApoA2基因的非翻译区， 与糖尿病有关。然而ApoA2血清水平分析 通过比浊法测定， 表明多态性导致表达水平的变异性 ApoA2因此，我们的数据并不表明ApoA2本身 是负责在1号染色体上观察到的连锁的基因。

A gene is considered a candidate gene for type 2 diabetes in Pimas if 1) it is associated with a diabetic phenotype in another population or 2) it has a physiologically relevant function and is positioned in a chromosomal region that is linked to diabetes. Candidate genes which have been analyzed to date include those genes which are associated with Mody in other populations. We identified several polymorphisms in the HNFl?, HNFlb, and HNF3b genes, but none were associated with early onset diabetes in Pimas. One polymorphism in HNFlb, however, predicts a non-conservative amino acid substitution within a critical region of the protein and therefore is being further investigated for functional variability in transfected cell lines. We have also analyzed candidate genes in an area on chromosome 1 linked to diabetes. No polymorphisms associated with diabetes were identified in the pyruvate kinase or the retinoid X receptor gamma genes. We identified one polymorphism in the promoter and 4 polymorphisms in the 3? untranslated region of the ApoA2 gene which were modestly associated with diabetes. However analysis of ApoA2 serum levels by turbidimetric assays in individuals with these variants did not suggest the polymorphisms result in variability in expression levels of ApoA2. Therefore, our data does not suggest that ApoA2 itself is the gene responsible for the linkage observed on chromosome 1.