Tumor necrosis factor alpha and interleukin 10 promoter region polymorphisms and risk of late-onset Alzheimer disease.
BACKGROUND
Functional polymorphisms in tumor necrosis factor alpha (TNF-alpha) and interleukin 10 (IL-10) can affect immune response, inflammation, tissue injury, and possibly the susceptibility to Alzheimer disease (AD).


OBJECTIVE
To evaluate the association between promoter region polymorphisms in the TNF-alpha and IL-10 genes and risk of late-onset AD in older white subjects.


METHODS
Community-based case-control study.


METHODS
Group Health Cooperative of Puget Sound.


METHODS
White subjects (n = 265) meeting criteria for probable or definite AD (cases) and white control subjects (n = 347) (controls).


METHODS
Genotyping results for TNF-alpha, IL-10, and apolipoprotein E (APOE) genotyping.


RESULTS
The TNF-alpha -863 A allele was associated with reduced odds of developing AD, and the test for trend suggested that having 2 copies of the A allele further reduces the risk (odds ratios [C/C, reference], 0.66 for C/A and 0.58 for A/A; P = .04). Because of linkage disequilibrium in the TNF-alpha region, we constructed promoter region haplotypes as defined by single nucleotide polymorphisms at positions -863 and -308. Based on knowledge of TNF-alpha protein production, we ordered the haplotypes based on apparent increasing transcriptional activity. After adjusting for age, education, and the presence of the APOE epsilon4 genotype, the test for trend showed increasing odds of AD with increasing transcriptional activity (P = .02). The IL-10 -1082 and IL-10 -592 allele and genotype frequencies were not significantly different between cases and controls.


CONCLUSIONS
Variation in the TNF-alpha promoter region, or possibly polymorphisms in nearby genes, could affect cerebral inflammatory response and the risk of late-onset AD.
Ramos
Erin M
EM
Institute for Public Health Genetics, Department of Medicine, University of Washington, Seattle, WA, USA.
Lin
Ming-Tesh
MT
Larson
Eric B
EB
Maezawa
Izumi
I
Tseng
Li-Hui
LH
Edwards
Karen L
KL
Schellenberg
Gerard D
GD
Hansen
John A
JA
Kukull
Walter A
WA
Jin
Lee-Way
LW
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10