Association between variants in IDE-KIF11-HHEX and plasma amyloid β levels.
Genetic linkage and association studies in late-onset Alzheimer's disease (LOAD) or its endophenotypes have pointed to several regions on chromosome 10q, among these the ∼ 250 kb linkage disequilibrium (LD) block harboring the genes IDE, KIF1, and HHEX. We explored the association between variants in the genomic region harboring the IDE-KIF11-HHEX complex with plasma Aβ40 and Aβ42 levels in a case-control cohort of Caribbean Hispanics. First, we performed single marker linear regression analysis relating the individual single nucleotide polymorphisms (SNPs) with plasma Aβ40 and Aβ42 levels. Then we performed 3-SNP sliding window haplotype analyses, correcting all analyses for multiple testing. Out of 32 SNPs in this region, 3 SNPs in IDE (rs2421943, rs12264682, rs11187060) were associated with plasma Aβ40 or Aβ42 levels in single marker and haplotype analyses after correction for multiple testing. All these SNPs lie within the same LD block, and are in LD with the previously reported haplotypes. Our findings provide support for an association in the IDE region on chromosome 10q with Aβ40 and 42 levels.
Reitz
Christiane
C
The Taub Institute for Research on Alzheimer's Disease and Aging Brain, Columbia University, New York, NY 10032, USA.
Cheng
Rong
R
Schupf
Nicole
N
Lee
Joseph H
JH
Mehta
Pankaj D
PD
Rogaeva
Ekaterina
E
St George-Hyslop
Peter
P
Mayeux
Richard
R
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000097:blood*; D017691:Caribbean Region; D016022:Case-Control Studies; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D058068:Endophenotypes; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006630:Hispanic or Latino / Q000208:ethnology; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007339:Insulysin / Q000235:genetics*; D016547:Kinesins / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics*; D008297:Male; D010446:Peptide Fragments / Q000097:blood*; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D014157:Transcription Factors / Q000235:genetics*
D016229:Amyloid beta-Peptides; C078492:HHEX protein, human; D018398:Homeodomain Proteins; C470243:KIF11 protein, human; D010446:Peptide Fragments; D014157:Transcription Factors; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D007339:Insulysin; D016547:Kinesins