Tumour necrosis factor-alpha gene polymorphisms and Alzheimer's disease |
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Authors: | Culpan Doris MacGowan Sian H Ford Julia M Nicoll James A R Griffin W Sue Dewar Deborah Cairns Nigel J Hughes Anthony Kehoe Patrick G Wilcock Gordon K |
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Affiliation: | Department of Care of the Elderly, University of Bristol, John James Buildings, Frenchay Hospital, Frenchay, Bristol, BS16 1LE, UK. doris.culpan@bristol.ac.uk |
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Abstract: | Recent findings suggest that production of pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha), 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-alpha gene to respectively examine TNF-alpha 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-alpha 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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