Open Access Research article

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

Jasmin Bartl1*, Claus-Jürgen Scholz2, Margareta Hinterberger3, Susanne Jungwirth3, Ildiko Wichart3, Michael K Rainer3, Susanne Kneitz2, Walter Danielczyk3, Karl H Tragl3, Peter Fischer34, Peter Riederer13 and Edna Grünblatt135

Author Affiliations

1 Department of Psychiatry, Psychosomatic and Psychotherapy, University Hospital of Wuerzburg, Fuechsleinstr. 15, D-97080 Wuerzburg, Germany

2 IZKF Laboratory for Microarray Applications, University Hospital of Wuerzburg, Versbacher Str. 7, D-97078 Wuerzburg, Germany

3 Ludwig Boltzmann Society, L. Boltzmann Institute of Aging Research, Vienna, Austria

4 Department of Psychiatry, Social Medical Center, Danube Hospital, Langobardenstraße 122, A-1220 Vienna, Austria

5 Hospital of Child and Adolescent Psychiatry, University of Zurich, Neumuensterallee 9, CH-8032 Zurich, Switzerland

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BMC Medical Genetics 2011, 12:151  doi:10.1186/1471-2350-12-151

Published: 22 November 2011



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.


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.


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.


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.