Tumour necrosis factor-?gene polymorphisms and Alzheimer's disease

Culpan, Doris, MacGowan, Sian H., Ford, Julia M., Nicoll, James A., Griffin, W. Sue, Dewar, Deborah, Cairns, Nigel J., Hughes, Anthony, Kehoe, Patrick G. and Wilcock, Gordon K. (2003) Tumour necrosis factor-?gene polymorphisms and Alzheimer's disease. Neuroscience Letters, 350 (1), 61-65. (doi:10.1016/S0304-3940(03)00854-1).

Abstract

Recent findings suggest that production of pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-?), is increased in the brains of people with Alzheimer's disease (AD). We used direct sequencing methods on a section of the enhancer/promoter region and on a smaller fragment located 10.5 kb upstream of the TNF-? gene to respectively examine TNF-? polymorphisms and TNF-a and -b microsatellite alleles in a cohort of 235 post-mortem confirmed AD and 130 control cases. None of the TNF-? point mutations or microsatellite alleles investigated proved to be independent risk factors for AD. However, when ?308/A, ?238/G and TNF-a2 were examined as a 2-1-2 haplotype, we observed that the absence of that haplotype was significantly associated with AD (P=0.014, Fisher's exact test) suggesting that the 2-1-2 haplotype may be protective against AD.

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Contributors

Author: James A. Nicoll

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