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

Abstract

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 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 ε4 there was no association of poly-T repeat length with age of onset. Neither APOE ε4 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.