Tumor necrosis factor α and interleukin 10 promoter region polymorphisms and risk of late-onset Alzheimer disease

Erin M. Ramos, Ming-Tseh Lin, Eric B. Larson, Izumi Maezawa, Li Hui Tseng, Karen L. Edwards, Gerard D. Schellenberg, John A. Hansen, Walter A. Kukull, Lee Way Jin

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1165-1169
Number of pages5
JournalArchives of Neurology
Volume63
Issue number8
DOIs
StatePublished - Aug 2006
Externally publishedYes

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Genetic Promoter Regions
Interleukin-10
Alzheimer Disease
Tumor Necrosis Factor-alpha
Haplotypes
Alleles
Odds Ratio
Genotype
Apolipoprotein E4
Linkage Disequilibrium
Apolipoproteins E
Onset
Polymorphism
Alzheimer's Disease
Gene Frequency
Genes
Single Nucleotide Polymorphism
Case-Control Studies
Outcome Assessment (Health Care)
Inflammation

ASJC Scopus subject areas

  • Neuroscience(all)

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Tumor necrosis factor α and interleukin 10 promoter region polymorphisms and risk of late-onset Alzheimer disease. / Ramos, Erin M.; Lin, Ming-Tseh; Larson, Eric B.; Maezawa, Izumi; Tseng, Li Hui; Edwards, Karen L.; Schellenberg, Gerard D.; Hansen, John A.; Kukull, Walter A.; Jin, Lee Way.

In: Archives of Neurology, Vol. 63, No. 8, 08.2006, p. 1165-1169.

Research output: Contribution to journalArticle

Ramos, EM, Lin, M-T, Larson, EB, Maezawa, I, Tseng, LH, Edwards, KL, Schellenberg, GD, Hansen, JA, Kukull, WA & Jin, LW 2006, 'Tumor necrosis factor α and interleukin 10 promoter region polymorphisms and risk of late-onset Alzheimer disease', Archives of Neurology, vol. 63, no. 8, pp. 1165-1169. https://doi.org/10.1001/archneur.63.8.1165
Ramos, Erin M. ; Lin, Ming-Tseh ; Larson, Eric B. ; Maezawa, Izumi ; Tseng, Li Hui ; Edwards, Karen L. ; Schellenberg, Gerard D. ; Hansen, John A. ; Kukull, Walter A. ; Jin, Lee Way. / Tumor necrosis factor α and interleukin 10 promoter region polymorphisms and risk of late-onset Alzheimer disease. In: Archives of Neurology. 2006 ; Vol. 63, No. 8. pp. 1165-1169.
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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-Tseh

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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