Tumour necrosis factor-alpha gene polymorphisms and Alzheimer's disease.
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.
Culpan
Doris
D
Department of Care of the Elderly, University of Bristol, John James Buildings, Frenchay Hospital, Frenchay, Bristol, BS16 1LE, UK. doris.culpan@bristol.ac.uk
MacGowan
Sian H
SH
Ford
Julia M
JM
Nicoll
James A R
JA
Griffin
W Sue
WS
Dewar
Deborah
D
Cairns
Nigel J
NJ
Hughes
Anthony
A
Kehoe
Patrick G
PG
Wilcock
Gordon K
GK
D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine / Q000235:genetics; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D004742:Enhancer Elements, Genetic; D005260:Female; D005787:Gene Frequency; D005998:Glycine / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D000409:Alanine; D005998:Glycine