Interleukin-1A polymorphism is not associated with late onset Alzheimer's disease

Department of Pharmacology, School of Medicine, Aristotle University, 540 06, Thessaloniki, Greece.
Neuroscience Letters (Impact Factor: 2.03). 05/2002; 323(1):81-3. DOI: 10.1016/S0304-3940(02)00114-3
Source: PubMed


Over the past few years, association studies have proposed a number of potential genetic risk factors for Alzheimer's disease (AD). With the exception of the varepsilon4 allele of the apolipoprotein E gene, whose association with the late onset type of AD (LOAD) has been confirmed, the relative significance of most of these associations is still in question. A polymorphism in the interleukin-1A gene (IL-1A2) has been suggested as a risk factor for the early onset as well as for LOAD. In this study, the distribution of IL-1A alleles was examined in a cohort of predominantly LOAD patients and in control individuals. No significant difference was detected in genotype or allele frequencies (odds ratios of 0.929 and 0.743, respectively; P>0.5). We conclude that IL-1A genotype is not a major risk factor for LOAD.

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    • "Among common population polymorphisms recently associated with AD, such as those for the genes of ␣ 2 -macroglobulin [12], ␣ 1 -antichymotrypsin [25], angiotensin-converting enzyme (ACE) [27], methylenetetrahydrofolate reductase (MTHFR) [50] [58] and others, new evidence suggests that susceptibility to AD may be associated to polymorphisms in genes that affect the inflammatory cascade [36]. Recently, in fact, polymorphisms in the genes coding for the proinflammatory interleukins-1␣ (IL-1␣) and ␤ (IL-1␤) have been associated with both late-and early-onset AD [13,20,22,43,49], although other studies did not confirm this association [15] [17] [30] [39] [44]. "
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    ABSTRACT: Increased risk of Alzheimer's disease (AD) has been associated with polymorphisms in the IL-1 gene cluster, and in particular with the IL-1alpha-889 T/T genotype. However, this association is still unclear, and needs further investigation. In order to clarify the role of these polymorphisms in the complex pathogenesis of AD we examined genotype and haplotype frequencies of the two C-to-T SNPs at position -889 and -551 in the IL-1alpha and IL-1beta genes, respectively, and of the 86 bp VNTR intron-2 polymorphisms in the IL-1Ra gene. The analysis was performed in two genetically and diagnostically distinct groups of sporadic AD from Italy and the USA. In the Italian group a significant association between the IL-1alpha-889 T/T genotype and AD (OR=3.022, 95% CI: 1.001-9.119) was found, whereas no difference was found in the group from the USA. Results were also compared with previously published studies that analyzed the same IL-1 polymorphisms in AD. In both groups, the analysis of the estimated haplotypes shows that AD patients and controls who carry the IL-1beta-511 C allele, were also more frequently carriers of the IL-1Ra 1 allele (haplotypes -C-1). The total frequency of the two -C-1 haplotypes (C-C-1 plus T-C-1) was about one half of the total frequency of the eight estimated haplotypes. This was confirmed by significant linkage disequilibrium between these two loci in both the Italian and USA groups. In the Italian group a weak association of the T-C-2 haplotype with the disease (OR=1.648, 95% CI: 1.519-1.788) was also found, whereas in the USA group no difference was found. Although ours and other published data on different samples of Caucasian and non-Caucasian AD show a great heterogeneity in the frequencies of the IL-1alpha-889, the IL-1beta-511 and the IL-1Ra VNTR gene polymorphisms, we confirm the role of the IL-1alpha-889 T/T genotype as a risk factor for sporadic AD, and show the presence of an allelic association between IL-1beta C and IL-1Ra 1 alleles in both the Italian and the USA groups, confirmed by the presence of significant levels of linkage disequilibrium between these two loci.
    Neurobiology of Aging 05/2005; 26(4):455-64. DOI:10.1016/j.neurobiolaging.2004.04.001 · 5.01 Impact Factor
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    • "The frequency of the IL-1A T allele in our controls, 7.5%, was much lower than those of Caucasians which were reported to be 17.8 % -33% (Du et al., 2000; Grimaldi et al., 2000; Minster et al., 2000; Nicoll et al., 2000; Rebeck, 2000; Kolsch et al., 2001; Combarros et al., 2002; Fidani et al., 2002; Green et al., 2002; Hedley et al., 2002; Pirskanen et al., 2002), but it was similar to those of East Asians (7.1%-11.3%; Ki et al., 2001; Kuo et al., 2003; Tsai et al., 2003). "
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    ABSTRACT: To examine whether the IL-1A (-889) polymorphism associates with a risk for Alzheimer's disease (AD) and acts interactively with the apolipoprotein (APOE) ε4 in the development of AD, we performed genotype analyses of the IL-1A and the APOE of the 102 Korean AD patients and 200 Korean non-demented controls. We failed to detect a significant difference in genotypic and allelic frequencies of IL-1A between the AD group and control group. No overexpression of the IL-1A C/T genotype and IL-1A T allele was found when we analyzed the late-onset and early-onset patients, separately. There was no significant genetic interaction between IL-1A polymorphism and the APOE polymorphism. In conclusion, the IL-1A polymorphism did not contribute to the development of AD independently or interactively with the APOE ε4 allele in Koreans.
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    ABSTRACT: Epidemiological studies have evaluated the association between interleukin-1 (IL-1)α C(−889)T polymorphism and Alzheimer’s disease (AD), but the results remain inconclusive. This meta-analysis was, therefore, designed to clarify these controversies. Systematic searches of electronic databases Embase, PubMed, and Web of Science as well as hand searching of the references of identified articles and the meeting abstracts were performed. Statistical analyses were performed using software Review Manager (Version 5.1.2) and Stata (Version 11.0). The pooled odds ratios (ORs) with 95 % confidence intervals (95 % CIs) were calculated. A total of 28 publications including 29 studies were involved. There was a significant association between IL-1α C(−889)T polymorphism and AD (for T allele vs. C allele: OR = 1.14, 95 % CI = 1.07–1.21; for T/T vs. C/C: OR = 1.39, 95 % CI = 1.18–1.63; for dominant model: OR = 1.13, 95 % CI = 1.04–1.22; and for recessive model: OR = 1.39, 95 % CI = 1.20–1.60). Significant association was found for Asians, Caucasians, and early-onset Alzheimer’s disease (EOAD) but for late-onset Alzheimer’s disease (LOAD). This meta-analysis indicates that there is a significant association between IL-1α C(−889)T polymorphism and AD as well as EOAD.
    Journal of Neural Transmission 03/2012; 120(3). DOI:10.1007/s00702-012-0867-y · 2.40 Impact Factor
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