TY - JOUR
T1 - Tumor necrosis factor α and interleukin 10 promoter region polymorphisms and risk of late-onset Alzheimer disease
AU - Ramos, Erin M.
AU - Lin, Ming Tesh
AU - Larson, Eric B.
AU - Maezawa, Izumi
AU - Tseng, Li Hui
AU - Edwards, Karen L.
AU - Schellenberg, Gerard D.
AU - Hansen, John A.
AU - Kukull, Walter A.
AU - Jin, Lee Way
PY - 2006/8
Y1 - 2006/8
N2 - Background: Functional polymorphisms in tumor necrosis factor α (TNF-α) 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-α and IL-10 genes and risk of late-onset AD in older white subjects. Design: Community-based case-control study. Setting: Group Health Cooperative of Puget Sound. Participants: White subjects (n=265) meeting criteria for probable or definite AD (cases) and white control subjects (n=347) (controls). Main Outcome Measures: Genotyping results for TNF-α, IL-10, and apolipoprotein E (APOE) genotyping. Results: The TNF-α -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-α region, we constructed promoter region haplotypes as defined by single nucleotide polymorphisms at positions -863 and -308. Based on knowledge of TNF-α protein production, we ordered the haplotypes based on apparent increasing transcriptional activity. After adjusting for age, education, and the presence of the APOE ε4 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. Conclusion: Variation in the TNF-α promoter region, or possibly polymorphisms in nearby genes, could affect cerebral inflammatory response and the risk of late-onset AD.
AB - Background: Functional polymorphisms in tumor necrosis factor α (TNF-α) 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-α and IL-10 genes and risk of late-onset AD in older white subjects. Design: Community-based case-control study. Setting: Group Health Cooperative of Puget Sound. Participants: White subjects (n=265) meeting criteria for probable or definite AD (cases) and white control subjects (n=347) (controls). Main Outcome Measures: Genotyping results for TNF-α, IL-10, and apolipoprotein E (APOE) genotyping. Results: The TNF-α -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-α region, we constructed promoter region haplotypes as defined by single nucleotide polymorphisms at positions -863 and -308. Based on knowledge of TNF-α protein production, we ordered the haplotypes based on apparent increasing transcriptional activity. After adjusting for age, education, and the presence of the APOE ε4 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. Conclusion: Variation in the TNF-α promoter region, or possibly polymorphisms in nearby genes, could affect cerebral inflammatory response and the risk of late-onset AD.
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U2 - 10.1001/archneur.63.8.1165
DO - 10.1001/archneur.63.8.1165
M3 - Article
C2 - 16908746
AN - SCOPUS:33747203455
SN - 0003-9942
VL - 63
SP - 1165
EP - 1169
JO - Archives of neurology
JF - Archives of neurology
IS - 8
ER -