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

德国 2 型糖尿病 (T2DM) 的分子遗传学：德国促成 2 型糖尿病发展的基因/多态性

• 批准号: 5310372
• 负责人: Professor Dr. Heinz-Erich Wichmann
• 金额: --
• 依托单位: Abteilung Molekulare Humangenetik (aufgelöst)
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2001
• 资助国家: 德国
• 起止时间: 2000-12-31 至 2003-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5310372?language=en
• 关键词: Molecular; genetics; type; diabetes; T2DM

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.

该项目的目的是识别和表征与德国2型糖尿病(T2 DM)发病相关的序列变异。在第一个资助期间，我们对394对患有T2 DM的受影响同胞对(ASP)进行了全基因组微卫星标记扫描。初步分析发现3号染色体上有3个易感基因座(2点LOD2.30/D3S3050，P=0.001；Z值1.00)、16号染色体(2点LOD值1.01/D16S403，P=0.023；Z值1.56)、2号染色体(2点8，P=0.012)。为了确认和完成作图，我们将对来自维尔茨堡的537和116个ASP以及来自奥格斯堡的355个ASP另外三个样本进行基因分型。我们将阐明在初始和复制样本中负责连锁的家系。对于荟萃分析，我们将结合我们的数据和来自雷根斯堡的618名患有心肌梗死的ASP的基因组扫描。我们将在贡献最大的家庭中筛选链接地区内的所有可用的SNP。相关的SNP将在维尔茨堡的所有ASP、600个TDT家庭(AUGC-FAM)和2000例病例和2000名对照的优秀表型样本(AUGC-病例对照)中进行检测。可以在奥格斯堡样本中分析亚型(心肌梗死、高血压和肾病)。T2 DM变异体的鉴定和功能鉴定将有助于更好地了解这种疾病的分子基础，从而为糖尿病的新的预防和治疗方法提供科学基础。