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 language | English |
|---|---|
| Pages (from-to) | 480-483 |
| Number of pages | 4 |
| Journal | Neurology |
| Volume | 55 |
| Issue number | 4 |
| State | Published - 2000 |
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ASJC Scopus subject areas
- Neuroscience(all)
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Association of an interleukin 1α polymorphism with Alzheimer's disease. / Du, Yansheng; Dodel, R. C.; Eastwood, B. J.; Bales, K. R.; Gao, F.; Lohmüller, F.; Müller, U.; Kurz, A.; Zimmer, R.; Evans, R. M.; Hake, Ann; Gasser, T.; Oertel, W. H.; Griffin, W. S T; Paul, S. M.; Farlow, Martin.
In: Neurology, Vol. 55, No. 4, 2000, p. 480-483.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Association of an interleukin 1α polymorphism with Alzheimer's disease
AU - Du, Yansheng
AU - Dodel, R. C.
AU - Eastwood, B. J.
AU - Bales, K. R.
AU - Gao, F.
AU - Lohmüller, F.
AU - Müller, U.
AU - Kurz, A.
AU - Zimmer, R.
AU - Evans, R. M.
AU - Hake, Ann
AU - Gasser, T.
AU - Oertel, W. H.
AU - Griffin, W. S T
AU - Paul, S. M.
AU - Farlow, Martin
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
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M3 - Article
VL - 55
SP - 480
EP - 483
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 4
ER -