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.
Tumour necrosis factor-?gene polymorphisms and Alzheimer's disease
Neuroscience Letters, 350, (1), . (doi:10.1016/S0304-3940(03)00854-1).
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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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