Document Detail


Association of IL-1 RN*2 allele and methionine synthase 2756 AA genotype with dementia severity of sporadic Alzheimer's disease.
MedLine Citation:
PMID:  15201366     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Genetic polymorphisms of APO-E, homocysteine, and the IL-1 gene cluster (IL-1A, IL-1B, receptor antagonist IL-1RN) are associated with sporadic Alzheimer's disease and may involve interdependent pathways of neuronal toxicity. OBJECTIVE: To determine whether these polymorphisms and the genetic determinants of homocysteine (methylenetetrahydrofolate reductase, MTHFR; methionine synthase, MTR; transcobalamin, TC) are associated with an increased risk of severe dementia in Alzheimer's disease. METHODS: 152 patients with Alzheimer's disease and 136 controls were studied. The association of occurrence and dementia severity (Reisberg score <6 and >or=6) of Alzheimer's disease with APO-E, IL-1A, IL-1B, IL-1RN, MTHFR677 C-->T and 1298A-->C, MTR 2756 A-->G, and TC 776 C-->G polymorphisms was evaluated by multivariate logistic regression analysis after adjustment for age, sex, and age of onset of Alzheimer's disease. RESULTS: IL-1A TT and IL-1B CT/TT associated genotypes were at risk of Alzheimer's disease (odds ratio 4.80 (95% confidence interval, 1.32 to 17.40), p = 0.017); the MTR 2756 AA genotype was at risk of severe dementia (OR 2.97 (1.23 to 7.21), p = 0.016); IL-1 RN*2 was protective (OR 0.28, (0.11 to 0.69), p = 0.006). Allele epsilon4 of the APO-E and IL-1B CC genotypes increased the risk of severe Alzheimer's disease associated with the MTR 2756 AA genotype by 3.3-fold and 1.5-fold, respectively. CONCLUSIONS: Distinct determinants of the IL-1 gene cluster are related to the generation and progression of Alzheimer's disease. MTR only influences progression of the disease, which may be enhanced by carriage of allele epsilon4 of APO-E.
Authors:
P Bosco; R-M Guéant-Rodríguez; G Anello; A Romano; B Namour; R S Spada; F Caraci; G Tringali; R Ferri; J-L Guéant
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of neurology, neurosurgery, and psychiatry     Volume:  75     ISSN:  0022-3050     ISO Abbreviation:  J. Neurol. Neurosurg. Psychiatr.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-06-17     Completed Date:  2004-08-10     Revised Date:  2008-11-20    
Medline Journal Info:
Nlm Unique ID:  2985191R     Medline TA:  J Neurol Neurosurg Psychiatry     Country:  England    
Other Details:
Languages:  eng     Pagination:  1036-8     Citation Subset:  IM    
Affiliation:
IRCCS Associazione Oasi Maria SS, Institute for Research on Mental Retardation and Brain Aging, Troina, Italy.
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MeSH Terms
Descriptor/Qualifier:
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / genetics*
Aged
Alleles
Alzheimer Disease / genetics*
Apolipoproteins E / genetics
Case-Control Studies
Female
Genotype
Homocysteine / genetics
Humans
Interleukin-1 / classification,  genetics*
Italy
Male
Middle Aged
Polymorphism, Genetic / genetics
Severity of Illness Index
Chemical
Reg. No./Substance:
0/Apolipoproteins E; 0/Interleukin-1; 454-28-4/Homocysteine; EC 2.1.1.13/5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase

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