Interleukin-1A polymorphism is not associated with late onset Alzheimer's disease.
ABSTRACT 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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ABSTRACT: Objective. The genetic factors that predispose to the development of juvenile rheumatoid arthritis (JRA) and its complications are not completely understood. The cytokine interleukin-1 (IL-1) has been implicated in the pathogenesis of JRA and other inflammatory diseases. This study was performed to test whether polymorphisms of the IL-1α gene might be associated with JRA.Methods. We sequenced the 5' regulatory region (containing the promoter) of the human IL-1α gene in 18 normal subjects. This revealed a C (IL-1A1) to T (IL-1A2) transition polymorphism at position -889. We studied the frequencies of both alleles in patients with JRA (n = 269) and controls (n = 99).Results. An increased gene carriage of IL-1A2 was found in patients with early-onset, pauciarticular JRA (EOPA-JRA; n = 103) compared with controls (0.66 versus 0.49; P = 0.01, odds ratio [OR] = 2.1). Within this subset of JRA, the association with IL-1A2 was particularly strong in the patients in whom chronic iridocyclitis developed (n = 28) compared with those without chronic iridocyclitis (0.89 versus 0.57; P = 0.002, OR = 6.2). Within the group of EOPA-JRA patients, IL-1A2 was also associated with elevation of the erythrocyte sedimentation rate (P < 0.0025).Conclusion. This is the first report of a cytokine gene association with JRA, and we conclude that IL-1α itself, or a gene for which the IL-1α polymorphism is a marker, may contribute to the pathogenesis of EOPA-JRA and the ocular complications found in this group.Arthritis & Rheumatology 01/1995; 38(2):221 - 228. · 7.48 Impact Factor
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ABSTRACT: Interleukin 1, an immune response-generated cytokine that stimulates astrocyte proliferation and reactivity (astrogliosis), was present in up to 30 times as many glial cells in tissue sections of brain from patients with Down syndrome and Alzheimer disease compared with age-matched control subjects. Most interleukin 1-immunoreactive glia in Down syndrome and Alzheimer disease were classified as microglia. The number of interleukin 1 immunoreactive neurons did not appear to differ in Down syndrome and Alzheimer disease compared with control brain. Numerous temporal lobe astrocytes in Alzheimer disease and postnatal Down syndrome were intensely interleukin 1-, S-100-, and glial fibrillary acidic protein-immunoreactive and had reactive structure. Interleukin 1 levels in Alzheimer disease temporal lobe homogenates were elevated, as were the levels of S-100 and glial fibrillary acidic protein, two proteins reportedly elevated in reactive astrocytes. These data suggest that increased expression of S-100 in Down syndrome, resulting from duplication of the gene on chromosome 21 that encodes the beta subunit of S-100, may be augmented by elevation of interleukin 1. As a corollary, the astrogliosis in Alzheimer disease may be promoted by elevation of interleukin 1.Proceedings of the National Academy of Sciences 11/1989; 86(19):7611-5. · 9.74 Impact Factor
- Annals of Neurology - ANN NEUROL. 01/2000; 47(3):361-365.