Molecular genetics of type 2 diabetes (T2DM) in Germany: Genes / Polymorphisms fDeutschlands, die zur Entwicklung des Typ-2-Diabetes beitragen

该项目的目的是识别和表征在德国促进2型糖尿病（T2DM）发展的序列变异。在第一个资助期内，我们对394对患有T2DM的患病同胞（ASP）进行了微卫星标记的全基因组扫描。初步分析发现3号染色体上有3个易感位点（2点lod评分2.30/D3S3050, P = 0.001； Z评分1.00）、16号染色体上有3个易感位点（2点lod评分1.01/D16S403, P = 0.023； Z评分1.56）、2号染色体上有3个易感位点（2点8，P = 0.012）， 1号染色体上有2个有希望的易感位点。为了确认和精确定位，我们将对另外三个样本进行基因分型，分别为来自w<s:1> rzburg的537和116个asp以及来自Augsburg的355个asp。我们将阐明在初始和复制样本中负责连锁的家庭。为了进行荟萃分析，我们将把我们的数据与来自雷根斯堡的618例心肌梗死asp的基因组扫描相结合。我们将筛选贡献最大的家庭中关联区域内所有可用的snp。相关snp将在w<s:1> rzburg的所有asp、600个TDT家族（AUGC-fam）以及2000例和2000例对照（AUGC-case-control）的优秀表型样本中进行检测。亚表型（心肌梗死、高血压和肾病）可以在奥格斯堡样本中进行分析。T2 DM变异的鉴定和功能表征将有助于更好地了解该疾病的分子基础，从而为糖尿病预防和治疗的新方法提供科学依据。

The aim of this project is to identify and characterize sequence variants that contribute to the development of type 2 diabetes mellitus (T2DM) in Germany. We performed a genome-wide scan of microsatellite markers in 394 affected sib pairs (ASP) with T2DM during the first funding period. The scan revealed three susceptibility loci on chromosomes 3 (two point lod score 2.30/D3S3050, P = 0.001; Z score 1.00), 16 (two point lod score 1.01/D16S403, P = 0.023; Z score 1.56), 2 (two point 8, P = 0.012), and two promising loci on chromosome 1 in first preliminary analyses. For confirmation and finemapping we will genotype three additional samples of 537 and 116 ASPs from Würzburg and 355 ASPs from Augsburg. We will elucidate the families who were responsible for linkage in the initial and replication samples. For meta-analyses we will combine our data with a genome scan of 618 ASPs with myocardial infarction from Regensburg. We will screen all available SNPs within the linked regions in the most contributing families. Associated SNPs will be tested in all ASPs from Würzburg, in 600 TDT families (AUGC-fam) and in an excellently-phenotyped sample of 2,000 cases and 2,000 controls (AUGC-case-control). Subphenotypes (myocardial infarction, hypertension, and nephropathy) can be analysed in the Augsburg samples. The identification and functional characterization of variants for T2 DM will lead to a better understanding of the molecular basis of this disorder, thereby providing the scientific foundation for new approaches for prevention and treatment of diabetes.