Disorder-specific effects of polymorphisms at opposing ends of the Insulin Degrading Enzyme gene

作者：Bartl Jasmin^*; Scholz Claus Juergen; Hinterberger Margareta; Jungwirth Susanne; Wichart Ildiko; Rainer Michael K; Kneitz Susanne; Danielczyk Walter; Tragl Karl H; Fischer Peter; Riederer Peter; Gruenblatt Edna

来源：BMC Medical Genetics, 2011, 12: 151.

DOI：10.1186/1471-2350-12-151

Background: Insulin-degrading enzyme (IDE) is the ubiquitously expressed enzyme responsible for insulin and amyloid beta (A beta) degradation. IDE gene is located on chromosome region 10q23-q25 and exhibits a well-replicated peak of linkage with Type 2 diabetes mellitus (T2DM). Several genetic association studies examined IDE gene as a susceptibility gene for Alzheimer's disease (AD), however with controversial results.
Methods: We examined associations of three IDE polymorphisms (IDE2, rs4646953; IDE7, rs2251101 and IDE9, rs1887922) with AD, A beta(42) plasma level and T2DM risk in the longitudinal Vienna Transdanube Aging (VITA) study cohort.
Results: The upstream polymorphism IDE2 was found to influence AD risk and to trigger the A beta(42) plasma level, whereas the downstream polymorphism IDE7 modified the T2DM risk; no associations were found for the intronic variant IDE9.
Conclusions: Based on our SNP and haplotype results, we delineate the model that IDE promoter and 3' untranslated region/downstream variation may have different effects on IDE expression, presumably a relevant endophenotype with disorder-specific effects on AD and T2DM susceptibility.

• 出版日期2011-11-22