TY  - JOUR
A1  - Bartl, Jasmin
A1  - Scholz, Claus-Jürgen
A1  - Hinterberger, Margareta
A1  - Jungwirth, Susanne
A1  - Wichart, Ildiko
A1  - Rainer, Michael K.
A1  - Kneitz, Susanne
A1  - Danielczyk, Walter
A1  - Tragl, Karl H.
A1  - Fischer, Peter
A1  - Riederer, Peter
A1  - Grünblatt, Edna
T1  - Disorder-specific effects of polymorphisms at opposing ends of the Insulin Degrading Enzymegene
JF  - BMC Medical Genetics
N2  - 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.
KW  - Insulin Degrading Enzyme
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137744
VL  - 12
IS  - 151
ER  -