Association of an interleukin 1 alpha polymorphism with Alzheimer's disease

Neurology. 2000 Aug 22;55(4):480-3. doi: 10.1212/wnl.55.4.480.

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.

Conclusion: 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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / immunology
  • Apolipoprotein E4
  • Apolipoproteins E / genetics
  • Case-Control Studies
  • Cohort Studies
  • DNA Mutational Analysis
  • Female
  • Gene Frequency
  • Genetic Carrier Screening
  • Genotype
  • Heterozygote
  • Homozygote
  • Humans
  • Interleukin-1 / genetics*
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Genetic / genetics*
  • Risk Assessment

Substances

  • Apolipoprotein E4
  • Apolipoproteins E
  • Interleukin-1