title: Disorder-specific effects of polymorphisms at opposing ends of the Insulin Degrading Enzyme gene.
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.
authors: Department of Psychiatry, Psychosomatic and Psychotherapy, University Hospital of Wuerzburg, Fuechsleinstr, 15, D-97080 Wuerzburg, Germany. e_bartl_j@klinik.uni-wuerzburg.de
authors: Jasmin
authors: J
authors: Bartl
authors: Claus-Jürgen
authors: CJ
authors: Scholz
authors: Margareta
authors: M
authors: Hinterberger
authors: Susanne
authors: S
authors: Jungwirth
authors: Ildiko
authors: I
authors: Wichart
authors: Michael K
authors: MK
authors: Rainer
authors: Susanne
authors: S
authors: Kneitz
authors: Walter
authors: W
authors: Danielczyk
authors: Karl H
authors: KH
authors: Tragl
authors: Peter
authors: P
authors: Fischer
authors: Peter
authors: P
authors: Riederer
authors: Edna
authors: E
authors: Grünblatt
mesh_terms: D020413:3' Untranslated Regions; D000544:Alzheimer Disease / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000097:blood; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007339:Insulysin / Q000235:genetics*; D008137:Longitudinal Studies; D010446:Peptide Fragments / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012306:Risk
chemical_list: D020413:3' Untranslated Regions; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D007339:Insulysin