title: Interleukin-6 promoter polymorphism: risk and pathology of Alzheimer's disease.
abstract: Inflammatory and immune responses are involved in the pathogenesis of Alzheimer's disease (AD). Interleukin-6 (IL-6), an inflammatory cytokine, is thought to play a role in neurodegeneration of the central nervous system and has been associated with increased amyloid precursor protein expression in vitro and greater cognitive decline. Previously a C-174G polymorphism in the promoter of IL-6, which influences expression in vitro, has been found associated in some studies but not all. We investigated this polymorphism in a large independent UK sample of AD cases (n = 356) and controls (n 434) but found no association. We extended the study to genotype/phenotype correlations but found no correlation with age of onset (n = 338), brain amyloid load (n = 126) or Tau load (n = 101), brain microglial cell load (n = 65) or brain reactive astrocytes (n = 127). Our data do not support a pathogenic role in AD for the C-174G polymorphism in isolation.
authors.affiliation: Department of Psychiatry, University of Birmingham, Queen Elizabeth Psychiatric Hospital, Birmingham, B15 2QZ, UK.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Angela
authors.initials: A
authors.lastname: Hayes
authors.forename: Antonia
authors.initials: A
authors.lastname: Pritchard
authors.forename: Uma
authors.initials: U
authors.lastname: Thaker
authors.forename: M Sayeed
authors.initials: MS
authors.lastname: Haque
authors.forename: Helen
authors.initials: H
authors.lastname: Lemmon
authors.forename: Judith
authors.initials: J
authors.lastname: Harris
authors.forename: Alistair
authors.initials: A
authors.lastname: Cumming
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Lambert
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Chartier-Harlin
authors.forename: David
authors.initials: D
authors.lastname: St  Clair
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwatsubo
authors.forename: David M
authors.initials: DM
authors.lastname: Mann
authors.forename: Corinne L
authors.initials: CL
authors.lastname: Lendon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000276:immunology*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors
chemical_list: D015850:Interleukin-6