title: Association of alleles carried at TNFA -850 and BAT1 -22 with Alzheimer's disease.
abstract: 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 epsilon4 genotype. Semi-quantitative RT-PCR was also performed for BAT1 from RNA isolated from brain tissue from AD and control cases.
  
  
  RESULTS
  APOE epsilon4 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 epsilon4 genotype. Semi-quantitative mRNA analysis in human brain tissue showed elevated levels of BAT1 mRNA in frontal cortex of AD cases.
  
  
  CONCLUSIONS
  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.
authors: Centre of Excellence for Alzheimer's Disease Research and Care, Faculty of Computing, Health and Science, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Joondalup, 6027, WA, Australia. agnjec@cyllene.uwa.edu.au
authors: Anastazija
authors: A
authors: Gnjec
authors: Katarzyna J
authors: KJ
authors: D'Costa
authors: Simon M
authors: SM
authors: Laws
authors: Ross
authors: R
authors: Hedley
authors: Kelvin
authors: K
authors: Balakrishnan
authors: Kevin
authors: K
authors: Taddei
authors: Georgia
authors: G
authors: Martins
authors: Athena
authors: A
authors: Paton
authors: Giuseppe
authors: G
authors: Verdile
authors: Samuel E
authors: SE
authors: Gandy
authors: G Anthony
authors: GA
authors: Broe
authors: William S
authors: WS
authors: Brooks
authors: Hayley
authors: H
authors: Bennett
authors: Olivier
authors: O
authors: Piguet
authors: Patricia
authors: P
authors: Price
authors: Judith
authors: J
authors: Miklossy
authors: Joachim
authors: J
authors: Hallmayer
authors: Patrick L
authors: PL
authors: McGeer
authors: Ralph N
authors: RN
authors: Martins
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D001315:Australia; D001921:Brain / Q000378:metabolism / Q000473:pathology; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008285:Major Histocompatibility Complex; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; C487886:DDX39B protein, human; D053487:DEAD-box RNA Helicases