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

Y. Du, R. C. Dodel, B. J. Eastwood, K. R. Bales, F. Gao, F. Lohmüller, U. Müller, A. Kurz, R. Zimmer, R. M. Evans, A. Hake, T. Gasser, W. H. Oertel, W. S.T. Griffin, S. M. Paul, M. R. Farlow

Research output: Contribution to journalArticle

181 Scopus citations

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-1α gene (a C-to-T transition designated as IL-1A[-889] allele 2) may cause an overexpression of IL-1α, 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 ε4 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.

Original languageEnglish (US)
Pages (from-to)480-483
Number of pages4
JournalNeurology
Volume55
Issue number4
StatePublished - Sep 5 2000

ASJC Scopus subject areas

  • Clinical Neurology

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    Du, Y., Dodel, R. C., Eastwood, B. J., Bales, K. R., Gao, F., Lohmüller, F., Müller, U., Kurz, A., Zimmer, R., Evans, R. M., Hake, A., Gasser, T., Oertel, W. H., Griffin, W. S. T., Paul, S. M., & Farlow, M. R. (2000). Association of an interleukin 1α polymorphism with Alzheimer's disease. Neurology, 55(4), 480-483.