title: 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.
authors.affiliation: Department of Statistics, Carnegie Mellon University, Pittsburgh, PA, USA.
authors.forename: Su Hee
authors.initials: SH
authors.lastname: Chu
authors.forename: Kathryn
authors.initials: K
authors.lastname: Roeder
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ferrell
authors.forename: Bernie
authors.initials: B
authors.lastname: Devlin
authors.forename: Mary Ann A
authors.initials: MA
authors.lastname: DeMichele-Sweet
authors.forename: M Ilyas
authors.initials: MI
authors.lastname: Kamboh
authors.forename: Oscar L
authors.initials: OL
authors.lastname: Lopez
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sweet
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D011071:Poly T / Q000235:genetics*; D011618:Psychotic Disorders / Q000453:epidemiology* / Q000235:genetics*; D012307:Risk Factors
chemical_list: D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C400783:TOMM40 protein, human; D011071:Poly T