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

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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.