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

Departments of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, 46202, USA.
Neurology (Impact Factor: 8.25). 09/2000; 55(4):480-3.
Source: PubMed

ABSTRACT 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.
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.
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.
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.

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    ABSTRACT: The Interleukin-1A (IL-1A) -889C/T polymorphism has been reported to be associated with Alzheimer's disease (AD) susceptibility, but the results of these previous studies have been inconsistent. The aim of this study was to explore whether the IL-1A -889C/T polymorphism confers susceptibility to AD. All studies published up to July 2011 on the association between the IL-1A -889C/T polymorphism and AD risk were identified by searching electronic databases PubMed, Embase and Alzgene. The association between the IL-1A -889C/T polymorphism and AD risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). A total of 32 case-control studies including 7,046 AD cases and 7,534 controls were eventually identified. Overall, positive associations of the IL-1A -889C/T polymorphism with AD risk were found in allele comparison T versus C (OR = 1.019, 95% CI= 1.027-1.198), recessive model TT versus CT + CC (OR = 1.278, 95% CI = 1.073-1.522) and dominant model TT + CT versus CC (OR = 1.102, 95% CI = 1.013-1.200). In subgroup analysis stratified by ethnicity, significant associations were demonstrated in Caucasians but not in Asians. In subgroup analysis according to the age of onset, no significant association was detected. The present meta-analysis suggests that the IL-1A is a candidate gene for AD susceptibility. The IL-1A -889C/T889C/T polymorphism may be a risk factor for AD in Caucasians. Further investigations taking the APOE ε4 status and other confirmed genetic factors and potential gene-gene and gene-environmental interactions into consideration for this polymorphism should be conducted.
    Journal of Neurology 01/2012; 259(8):1519-29. · 3.58 Impact Factor
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    ABSTRACT: Background  Upon skin contact to irritants, interleukin-1 alpha (IL-1α) is released in the stratum corneum as a primary step of skin inflammation. Variations in the IL-1A gene have been shown to alter the expression of IL-1α. This may influence the susceptibility to skin inflammation and the development of irritant contact dermatitis (ICD). Objective  To determine effects of an IL1A-889 C/T polymorphism in view of susceptibility to develop irritant contact dermatitis. Methods  In a case-control study, 478 Caucasian patients with occupational ICD of the hands were genotyped for an IL1A-889 C/T polymorphism. Results were compared to 393 apprentices from the same high risk occupations (controls). Results  Trends of a protective effect of the C→T transition at position IL1A-889 were seen (OR = 0.81; 95% CI: 0.65-1.00). The genotype distribution for IL1A-889 was 52.2% wild type (C/C), 39.2% heterozygous (C/T) and 8.6% homozygous for variant allele (T/T) in patients and 46.0%, 42.7% and 11.4% in controls. Subgroup analysis, which took into account atopy status and exposure, did not reveal a significant effect of this polymorphism for an aberrant risk to acquire for ICD. Conclusion  Our study indicates a possible protective effect of the IL1A-889 C/T polymorphism regarding the development of ICD.
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    ABSTRACT: No clear consensus has been reached on the Interleukin-1A (IL-1A) -889C/T polymorphism and Alzheimer's disease (AD) risk. In this meta-analysis, 27 case-control studies were assessed to evaluate the possible association. Overall, positive associations of the IL-1A -889C/T polymorphism with AD risk were found in allele comparison T vs. C (OR = 1.09, 95% CI = 1.01-1.18), recessive model TT vs. CT + CC (OR = 1.21, 95% CI = 1.01-1.45), and homozygote comparison (TT vs. CC; OR = 1.32, 95% CI = 1.04-1.67). In subgroup analysis stratified by ethnicity, significant associations were demonstrated in Caucasians but not in Asians. In subgroup analysis according to the age of onset, the data showed a significant association in patients with late-onset AD in Caucasians but not in early-onset AD. In conclusion, this meta-analysis supports the idea that IL-1A -889C/T polymorphism is capable of causing AD and LOAD susceptibility in Caucasians but not in Asians.
    Journal of Neuroscience Research 04/2012; 90(9):1681-92. · 2.97 Impact Factor