Header

UZH-Logo

Maintenance Infos

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


Bartl, J; Scholz, C J; Hinterberger, M; Jungwirth, S; Wichart, I; Rainer, M K; Kneitz, S; Danielczyk, W; Tragl, K H; Fischer, P; Riederer, P; Grünblatt, E (2011). Disorder-specific effects of polymorphisms at opposing ends of the Insulin Degrading Enzyme gene. BMC Medical Genetics, 12:151.

Abstract

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.

Abstract

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.

Statistics

Citations

4 citations in Web of Science®
4 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

20 downloads since deposited on 10 Mar 2012
4 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Center for Child and Adolescent Psychiatry
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2011
Deposited On:10 Mar 2012 17:17
Last Modified:20 Aug 2017 19:13
Publisher:BioMed Central
ISSN:1471-2350
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/1471-2350-12-151
PubMed ID:22107728

Download

Download PDF  'Disorder-specific effects of polymorphisms at opposing ends of the Insulin Degrading Enzyme gene'.
Preview
Content: Published Version
Filetype: PDF
Size: 356kB
View at publisher
Licence: Creative Commons: Attribution 2.0 Generic (CC BY 2.0)