Journal
NEUROBIOLOGY OF AGING
Volume 33, Issue 1, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2010.07.005
Keywords
Amyloid beta; Alzheimer's disease; Genetics; Insulin-degrading enzyme
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Funding
- National Institute of Health and the National Institute on Aging [R37-AG15473, P01-AG07232]
- Paul B. Beeson Career Development Award [K23AG034550]
- Blanchette Hooker Rockefeller Foundation
- Banbury Fund
- Alzheimer Society of Canada
- Japan-Canada
- Canadian Institutes of Health Research
- Alzheimer Society of Ontario
- Howard Hughes Medical Institute
- Wellcome Trust
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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 similar to 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 A beta 40 and A beta 42 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 A beta 40 and A beta 42 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 A beta 40 or A beta 42 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 A beta 40 and 42 levels. (C) 2012 Elsevier Inc. All rights reserved.
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