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Glutathione S-transferase P1 and T1 gene polymorphisms predict longitudinal course and age at onset of Alzheimer disease.
Am J Geriatr Psychiatry 2007; 15(10):879-87AJ

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.

CONCLUSION

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+Show Affiliations

Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Rome, Italy. g.spalletta@hsantalucia.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17911365

Citation

Spalletta, Gianfranco, et al. "Glutathione S-transferase P1 and T1 Gene Polymorphisms Predict Longitudinal Course and Age at Onset of Alzheimer Disease." The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry, vol. 15, no. 10, 2007, pp. 879-87.
Spalletta G, Bernardini S, Bellincampi L, et al. Glutathione S-transferase P1 and T1 gene polymorphisms predict longitudinal course and age at onset of Alzheimer disease. Am J Geriatr Psychiatry. 2007;15(10):879-87.
Spalletta, G., Bernardini, S., Bellincampi, L., Federici, G., Trequattrini, A., Ciappi, F., ... Bossù, P. (2007). Glutathione S-transferase P1 and T1 gene polymorphisms predict longitudinal course and age at onset of Alzheimer disease. The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry, 15(10), pp. 879-87.
Spalletta G, et al. Glutathione S-transferase P1 and T1 Gene Polymorphisms Predict Longitudinal Course and Age at Onset of Alzheimer Disease. Am J Geriatr Psychiatry. 2007;15(10):879-87. PubMed PMID: 17911365.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glutathione S-transferase P1 and T1 gene polymorphisms predict longitudinal course and age at onset of Alzheimer disease. AU - Spalletta,Gianfranco, AU - Bernardini,Sergio, AU - Bellincampi,Lorenza, AU - Federici,Giorgio, AU - Trequattrini,Alberto, AU - Ciappi,Fabrizio, AU - Bria,Pietro, AU - Caltagirone,Carlo, AU - Bossù,Paola, PY - 2007/10/4/pubmed PY - 2008/1/3/medline PY - 2007/10/4/entrez SP - 879 EP - 87 JF - The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry JO - Am J Geriatr Psychiatry VL - 15 IS - 10 N2 - 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. CONCLUSION: 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. SN - 1064-7481 UR - https://www.unboundmedicine.com/medline/citation/17911365/Glutathione_S_transferase_P1_and_T1_gene_polymorphisms_predict_longitudinal_course_and_age_at_onset_of_Alzheimer_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/15/10/879 DB - PRIME DP - Unbound Medicine ER -