Journal
NEUROBIOLOGY OF AGING
Volume 32, Issue 12, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2011.06.016
Keywords
Apolipoprotein E (APOE) epsilon 4; Late-onset Alzheimer disease (LOAD); Psychosis; TOMM40; Variable length poly-T repeat sequence
Categories
Funding
- National Institute on Aging (NIA) [AG 027224, AG030653, AG 05133]
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Apolipoprotein E (APOE) epsilon 4 alleles increase the risk for late-onset Alzheimer disease (LOAD) and decrease the age of onset. Recently, sequencing the APOE region in a small sample of LOAD subjects identified a variable length poly-T repeat sequence in the nearby gene, TOMM40, which may affect age of onset. We genotyped the TOMM40 poly-T repeat using a novel statistical approach to refine the identification of allele length in 892 LOAD subjects and evaluated its effects on age of onset. Because psychosis in LOAD is a heritable phenotype which has shown conflicting associations with APOE genotype, we also evaluated the association of poly-T repeat length with psychosis. Poly-T repeat lengths had a trimodal distribution which differed between APOE genotype groups. After accounting for APOE epsilon 4 there was no association of poly-T repeat length with age of onset. Neither APOE epsilon 4 nor poly-T repeat length was associated with psychosis. Our findings do not support the association of poly-T repeat length with age of onset in LOAD. The clinical implications of this repeat length polymorphism remain to be elucidated. (C) 2011 Elsevier Inc. All rights reserved.
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