| Titre : | Association between polymorphism in regulatory region of gene encoding tumour necrosis factor alpha and risk of Alzheimer's disease and vascular dementia : a case-control study. (2001) |
| Auteurs : | Shauna-M MCCUSKER ; Martin-D CURRAN ; Kevin-B DYNAN ; Catriona-D MCCULLAGH ; Stephen-P MCLLROY ; Derek MIDDLETON ; Apeter PASSMORE ; Christopher-C PATTERSON ; Duncan-D URQUHART ; Department of Geriatric Medicine. Queen's University of Belfast. Belfast. GBR ; Northern Ireland Regional Tissue Typing Laboratory. Belfast. GBR |
| Type de document : | Article |
| Dans : | Lancet (The) (vol. 357, n° 9254, 2001) |
| Pagination : | 436-439 |
| Langues: | Anglais |
| Mots-clés : | Démence Alzheimer ; Royaume Uni ; Europe ; Hérédité ; Prévalence ; Epidémiologie ; Adulte ; Homme ; Système nerveux [pathologie] ; Vaisseau sanguin encéphale [pathologie] ; Appareil circulatoire [pathologie] ; Vaisseau sanguin [pathologie] ; Génétique |
| Résumé : | [BDSP. Notice produite par INIST R0xWArL4. Diffusion soumise à autorisation]. Background Deposition of bêta-amyloid in the brains of patients with Alzheimer's disease is thought to precede a chain of events that leads to an inflammatory response by the brain. We postulated that genetic variation in the regulatory region of the gene for the proinflammatory cytokine tumour necrosis factor a (TNF-a) leads to increased risk of Alzheimer's disease and vascular dementia. Methods A polymorphism in the regulatory region of the TNF-alpha gene was analysed in a case-control study. The polymorphism (C-850T) was typed in 242 patients with sporadic Alzheimer's disease, 81 patients with vascular dementia, 61 stroke patients without dementia, and 235 normal controls. These groups of individuals were also genotyped for the apolipoprotein E polymorphism, and the vascular dementia and stroke groups were typed at the HLA-DR locus. Findings The distribution of TNF-a genotypes in the vascular dementia group differed significantly from that in the stroke and normal control groups, giving an odds ratio of 2.51 (95% Cl 1.49-4.21) for the development of vascular dementia for individuals with a CT or TT genotype. Logistic regression analysis indicated that the possession of the T allele significantly increased the risk of Alzheimer's disease associated with carriage of the apolipoprotein E e4 allele (odds ratio 2.73 [1.68-4.44] for those with apolipoprotein E e4 but no TNF-a T, vs 4.62 [2.38-8.96] for those with apolipoprotein E e4 and TNF-a T ; p=0.03). (...) |
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