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Published on: November 16, 2011
Disorder-specific effects of polymorphisms at opposing ends of the Insulin Degrading Enzyme gene
Jasmin Bartl1, Claus-Jürgen Scholz, Margareta Hinterberger
1Department of Psychiatry, Psychosomatic and Psychotherapy, University Hospital of Wuerzburg, Fuechsleinstr, 15, D-97080 Wuerzburg, Germany. e_bartl_j@klinik.uni-wuerzburg.de
Background:
Insulin-degrading enzyme (IDE) is the ubiquitously expressed enzyme responsible for insulin and amyloid beta (Aβ) 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, Aβ42 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 Aβ42 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.
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