title: A homopolymer polymorphism in the TOMM40 gene contributes to cognitive performance in aging.
abstract: BACKGROUND
  A highly polymorphic T homopolymer was recently found to be associated with late-onset Alzheimer's disease risk and age of onset.
  
  
  OBJECTIVE
  To explore the effects of the polymorphic polyT tract (rs10524523, referred as '523') on cognitive performance in cognitively healthy elderly individuals.
  
  
  METHODS
  One hundred eighty-one participants were recruited from local independent-living retirement communities. Informed consent was obtained, and participants completed demographic questionnaires, a conventional paper-and-pencil neuropsychological battery, and the computerized Cambridge Neuropsychological Test Automated Battery (CANTAB). Saliva samples were collected for determination of the TOMM40 '523' (S, L, VL) and the apolipoprotein E (APOE) (ɛ2, 3, 4) genotypes. From the initial sample of 181 individuals, 127 were eligible for the association analysis. Participants were divided into three groups based on '523' genotypes (S/S, S/L-S/VL, and L/L-L/VL-VL/VL). Generalized linear models were used to evaluate the association between the '523' genotypes and neuropsychological test performance. Analyses were adjusted for age, sex, education, depression, and APOE ɛ4 status. A planned subanalysis was undertaken to evaluate the association between '523' genotypes and test performance in a sample restricted to APOE ɛ3 homozygotes.
  
  
  RESULTS
  The S homozygotes performed better, although not significantly, than the S/L-S/VL and the VL/L-L/VL-VL/VL genotype groups on measures associated with memory (CANTAB Paired Associates Learning, Verbal Recognition Memory free recall) and executive function (CANTAB measures of Intra-Extra Dimensional Set Shift). Follow-up analysis of APOE ɛ3 homozygotes only showed that the S/S group performed significantly better than the S/VL group on measures of episodic memory (CANTAB Paired Associates Learning and Verbal Recognition Memory free recall), attention (CANTAB Rapid Visual Information Processing latency), and executive function (Digit Symbol Substitution). The S/S group performed marginally better than the VL/VL group on Intra-Extra Dimensional Set Shift. None of the associations remained significant after applying a Bonferroni correction for multiple testing.
  
  
  CONCLUSIONS
  Results suggest important APOE-independent associations between the TOMM40 '523' polymorphism and specific cognitive domains of memory and executive control that are preferentially affected in early-stage Alzheimer's disease.
authors.affiliation: Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, NC, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Hayden
authors.forename: Jill M
authors.initials: JM
authors.lastname: McEvoy
authors.forename: Colton
authors.initials: C
authors.lastname: Linnertz
authors.forename: Deborah
authors.initials: D
authors.lastname: Attix
authors.forename: Maragatha
authors.initials: M
authors.lastname: Kuchibhatla
authors.forename: Ann M
authors.initials: AM
authors.lastname: Saunders
authors.forename: Michael W
authors.initials: MW
authors.lastname: Lutz
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Welsh-Bohmer
authors.forename: Allen D
authors.initials: AD
authors.lastname: Roses
authors.forename: Ornit
authors.initials: O
authors.lastname: Chiba-Falek
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D003072:Cognition Disorders / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C400783:TOMM40 protein, human