Tumour necrosis factor-alpha gene polymorphisms and Alzheimer's disease.

Journal article

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.

Authors: Culpan, D; MacGowan, S; Ford, J; Nicoll, J; Griffin, W

• Publication status: Published
• Journal: Neuroscience letters
• Volume: 350
• Issue: 1
• Pages: 61-65
• Publication date: 2003-10-01
• DOI: 10.1016/s0304-3940(03)00854-1
• EISSN: 1872-7972
• ISSN: 0304-3940
• Language: English
• Keywords: Case-Control Studies; Gene Frequency; Alleles; Aged; Alanine; Aged, 80 and over; Glycine; Alzheimer Disease; Promoter Regions, Genetic; Polymorphism, Genetic; Tumor Necrosis Factor-alpha; Enhancer Elements, Genetic; Microsatellite Repeats; Haplotypes; Cohort Studies; Lymphotoxin-alpha; Polymerase Chain Reaction; Humans; Male; Female