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

Recent findings suggest that production of pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-α), 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-α gene to respectively examine TNF-α 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-α 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.