title: Glutathione S-transferase P1 and T1 gene polymorphisms predict longitudinal course and age at onset of Alzheimer disease.
abstract: OBJECTIVE
  Oxidative stress has been suggested as a contributor of Alzheimer disease (AD) neurodegeneration, particularly in those patients with late-onset AD (LOAD). Therefore, the authors studied the effect of glutathione S-transferase (GST) P1-M1-T1 gene polymorphisms and their interactions with the apolipoprotein E (ApoE) epsilon4 allelic variant on the three-year longitudinal course of AD.
  
  
  METHODS
  Global cognitive level as measured by the Mini-Mental State Exam, basic activities of daily living (BADLs) as measured by the Physical Self-Maintenance Scale, and behavior as measured by the Neuropsychiatric Inventory, were assessed at baseline and after 1, 2, and 3 years in a sample of 99 LOAD patients. These subjects were drug naive and had undergone the first clinical examination for the diagnosis of AD.
  
  
  RESULTS
  A multiple regression analysis indicated that the presence of ApoE epsilon4 allelic variant or GSTT1 null phenotype predicted the faster age at onset of the illness (F = 5.76, df = 2, 96, p = 0.0043). Carriers of GSTP1 *C allelic variant had a faster decline in cognitive functions (repeated measures analysis of variance [ANOVA]: F = 4.00, df = 3, 285, p = 0.008) and in BADLs (repeated measures ANOVA: F = 5.27, df = 3, 285, p = 0.001). This faster decline was independent from ApoE epsilon4 allele possession. No effect of GST P1-M1-T1 polymorphisms was found on behavioral symptom severity.
  
  
  CONCLUSIONS
  These data are in line with the hypotheses that oxidative damage is a prominent feature in the clinical progression and the age at onset of LOAD.
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Rome, Italy. g.spalletta@hsantalucia.it
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Spalletta
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
authors.forename: Lorenza
authors.initials: L
authors.lastname: Bellincampi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Federici
authors.forename: Alberto
authors.initials: A
authors.lastname: Trequattrini
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ciappi
authors.forename: Pietro
authors.initials: P
authors.lastname: Bria
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.forename: Paola
authors.initials: P
authors.lastname: Bossù
mesh_terms: D000203:Activities of Daily Living / Q000145:classification; D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D018450:Disease Progression; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D011110:Polymorphism, Genetic / Q000235:genetics*; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012044:Regression Analysis
chemical_list: D053327:Apolipoprotein E4; C413545:glutathione S-transferase T1; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase