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TOMM40 poly-T repeat lengths, age of onset and psychosis risk in Alzheimer disease.


ABSTRACT: Apolipoprotein E (APOE) ?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 ?4 there was no association of poly-T repeat length with age of onset. Neither APOE ?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.

SUBMITTER: Chu SH 

PROVIDER: S-EPMC3192304 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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TOMM40 poly-T repeat lengths, age of onset and psychosis risk in Alzheimer disease.

Chu Su Hee SH   Roeder Kathryn K   Ferrell Robert E RE   Devlin Bernie B   DeMichele-Sweet Mary Ann A MA   Kamboh M Ilyas MI   Lopez Oscar L OL   Sweet Robert A RA  

Neurobiology of aging 20110805 12


Apolipoprotein E (APOE) ε4 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 ps  ...[more]

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