title: Association of an interleukin 1 alpha polymorphism with Alzheimer's disease.
abstract: BACKGROUND
  Retrospective epidemiologic studies suggest that individuals exposed to anti-inflammatory agents such as nonsteroidal anti-inflammatory drugs have a lower probability of developing AD as well as an older age at onset for the illness. Neuroinflammation may play an important role in the pathogenesis of AD. Interleukin 1 (IL-1), a potent proinflammatory cytokine, is colocalized immunohistochemically to neuritic plaques, a requisite neuropathologic feature for AD. A polymorphism in the 5'-flanking regulatory region at -889 of the IL-1 alpha gene (a C-to-T transition designated as IL-1A[-889] allele 2) may cause an overexpression of IL-1 alpha, a finding shown to be associated with inflammatory diseases. The IL-1A(-889) allele 2 polymorphism may be associated with AD pathogenesis.
  
  
  METHODS
  A total of 259 patients with AD and 192 nondemented control subjects were included from two different centers (Indianapolis, IN, and Munich, Germany). Genotyping for APOE alleles and IL-1A(-889) allele 2 was performed by PCR-based amplification followed by restrictive endonuclease digestion. Statistical analyses were conducted by center-, gender group-, and age group-stratified Mantel-Haenszel odds ratios, CI, and p values.
  
  
  RESULTS
  The allele frequency of IL-1A(-889) allele 2 was 46% in clinically diagnosed patients with probable AD versus 34% in control subjects from the combined centers.
  
  
  CONCLUSIONS
  The authors found an increased risk for AD with an estimated Mantel-Haenszel odds ratio of 1.68 (95% CI 1.1 to 2.6; p = 0.022) for heterozygous carriers and 7.2 (95% CI 2.0 to 24.5; p = 0.003) for individuals homozygous for IL-1A(-889) allele 2. They found no evidence for an interaction between the IL-1A and the apoE epsilon 4 polymorphisms (carriers and homozygotes), age, or gender with regard to conferred risk. The data strongly support an association between the IL-1A(-889) allele 2, especially in homozygotes, and later-onset AD.
authors.affiliation: Departments of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, 46202, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Du
authors.forename: R C
authors.initials: RC
authors.lastname: Dodel
authors.forename: B J
authors.initials: BJ
authors.lastname: Eastwood
authors.forename: K R
authors.initials: KR
authors.lastname: Bales
authors.forename: F
authors.initials: F
authors.lastname: Gao
authors.forename: F
authors.initials: F
authors.lastname: Lohmüller
authors.forename: U
authors.initials: U
authors.lastname: Müller
authors.forename: A
authors.initials: A
authors.lastname: Kurz
authors.forename: R
authors.initials: R
authors.lastname: Zimmer
authors.forename: R M
authors.initials: RM
authors.lastname: Evans
authors.forename: A
authors.initials: A
authors.lastname: Hake
authors.forename: T
authors.initials: T
authors.lastname: Gasser
authors.forename: W H
authors.initials: WH
authors.lastname: Oertel
authors.forename: W S
authors.initials: WS
authors.lastname: Griffin
authors.forename: S M
authors.initials: SM
authors.lastname: Paul
authors.forename: M R
authors.initials: MR
authors.lastname: Farlow
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000276:immunology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D018570:Risk Assessment
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D007375:Interleukin-1