Association of alleles carried at TNFA-850 and BAT1-22 with Alzheimer's disease

被引：25

作者：

Gnjec, Anastazija ^{[1
,2
]}

D'Costa, Katarzyna J. ^{[1
,2
]}

Laws, Simon M. ^{[1
,2
]}

Hedley, Ross ^{[1
,2
]}

Balakrishnan, Kelvin ^{[1
,2
]}

Taddei, Kevin ^{[1
,2
]}

Martins, Georgia ^{[1
,2
]}

Paton, Athena ^{[1
,2
]}

Verdile, Giuseppe ^{[1
,2
]}

Gandy, Samuel E. ^{[3
]}

Broe, G. Anthony ^{[4
]}

Brooks, William S. ^{[5
,6
]}

Bennett, Hayley ^{[4
]}

Piguet, Olivier ^{[4
]}

Price, Patricia ^{[5
,6
,7
,8
]}

Miklossy, Judith ^{[9
]}

Hallmayer, Joachim ^{[10
,11
]}

McGeer, Patrick L. ^{[9
]}

Martins, Ralph N. ^{[1
,2
]}

机构：

[1] Edith Cowan Univ, Sch Exercise Biomed & Hlth Sci, Ctr Excellence Alzheimers Dis Res & Care, Fac Comp Hlth & Sci, Joondalup, WA 6027, Australia

[2] Univ Western Australia, Hollywood Private Hosp, Sch Psychiat & Clin Neurosci, Sir James McCusker Alzheimers Dis Res Unit, Nedlands, WA 6009, Australia

[3] Mt Sinai Sch Med, New York, NY 10029 USA

[4] UNSW, Prince Wales Med Res Inst, Randwick, NSW 2031, Australia

[5] Univ Sydney, Ctr Educ & Res Aging, Concord, NSW 2139, Australia

[6] Concord Repatriat Gen Hosp, Concord, NSW 2139, Australia

[7] Univ Western Australia, Sch Surg & Pathol, Nedlands, WA 6009, Australia

[8] Royal Perth Hosp, Dept Clin Immunol & Biochem Genet, Perth, WA 6000, Australia

[9] Univ British Columbia, Dept Psychiat, Kinsmen Lab Neurol Res, Vancouver, BC V6T 1Z3, Canada

[10] Stanford Univ, Dept Psychiat, Ctr Narcolepsy, Stanford, CA 94305 USA

[11] Stanford Univ, Dept Psychiat, Dept Genet, Stanford, CA 94305 USA

来源：

JOURNAL OF NEUROINFLAMMATION | 2008年 / 5卷 / 1期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

D O I：

10.1186/1742-2094-5-36

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background: Inflammatory changes are a prominent feature of brains affected by Alzheimer's disease (AD). Activated glial cells release inflammatory cytokines which modulate the neurodegenerative process. These cytokines are encoded by genes representing several interleukins and TNFA, which are associated with AD. The gene coding for HLA-B associated transcript 1 (BAT1) lies adjacent to TNFA in the central major histocompatibility complex (MHC). BAT1, a member of the DEAD-box family of RNA helicases, appears to regulate the production of inflammatory cytokines associated with AD pathology. In the current study TNFA and BAT1 promoter polymorphisms were analysed in AD and control cases and BAT1 mRNA levels were investigated in brain tissue from AD and control cases. Methods: Genotyping was performed for polymorphisms at positions -850 and -308 in the proximal promoter of TNFA and position -22 in the promoter of BAT1. These were investigated singly or in haplotypic association in a cohort of Australian AD patients with AD stratified on the basis of their APOE epsilon 4 genotype. Semi-quantitative RT-PCR was also performed for BAT1 from RNA isolated from brain tissue from AD and control cases. Results: APOE epsilon 4 was associated with an independent increase in risk for AD in individuals with TNFA-850*2, while carriage of BAT1-22*2 reduced the risk for AD, independent of APOE epsilon 4 genotype. Semi-quantitative mRNA analysis in human brain tissue showed elevated levels of BAT1 mRNA in frontal cortex of AD cases. Conclusion: These findings lend support to the application of TNFA and BAT1 polymorphisms in early diagnosis or risk assessment strategies for AD and suggest a potential role for BAT1 in the regulation of inflammatory reactions in AD pathology.

引用

页数：10

共 46 条

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