9
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Replication of Association between ADAM33 Polymorphisms and Psoriasis

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Polymorphisms in ADAM33, the first gene identified in asthma by positional cloning, have been recently associated with psoriasis. No replication study of this association has been published so far. Data available in the French EGEA study (Epidemiological study on Genetics and Environment of Asthma, bronchial hyperresponsivensess and Atopy) give the opportunity to attempt to replicate the association between ADAM33 and psoriasis in 2002 individuals. Psoriasis (n = 150) has been assessed by questionnaire administered by an interviewer and a sub-sample of subjects with early-onset psoriasis (n = 74) has been identified based on the age of the subjects at time of interview (<40 years). Nine SNPs in ADAM33 and 11 SNPs in PSORS1 were genotyped. Association analysis was conducted by using two methods, GEE regression-based method and a likelihood-based method (LAMP program). The rs512625 SNP in ADAM33 was found associated with psoriasis at p = 0.01, the usual threshold required for replication (OR [95% CI] for heterozygotes compared to the reference group of homozygotes for the most frequent allele = 0.61 [0.42;0.89]). The rs628977 SNP, which was not in linkage disequilibrium with rs512625, was significantly associated with early-onset psoriasis (p = 0.01, OR [95% CI] for homozygotes for the minor allele compared to the reference group = 2.52 [1.31;4.86]). Adjustment for age, sex, asthma and a PSORS1 SNP associated with psoriasis in the EGEA data did not change the significance of these associations. This suggests independent effects of ADAM33 and PSORS1 on psoriasis. This is the first study that replicates an association between genetic variants in ADAM33 and psoriasis. Interestingly, the 2 ADAM33 SNPs associated with psoriasis in the present analysis were part of the 3-SNPs haplotypes showing the strongest associations in the initial study. The identification of a pleiotropic effect of ADAM33 on asthma and psoriasis may contribute to the understanding of these common immune-mediated diseases.

          Related collections

          Most cited references27

          • Record: found
          • Abstract: found
          • Article: not found

          Pathogenesis and clinical features of psoriasis.

          Psoriasis, a papulosquamous skin disease, was originally thought of as a disorder primarily of epidermal keratinocytes, but is now recognised as one of the commonest immune-mediated disorders. Tumour necrosis factor alpha, dendritic cells, and T-cells all contribute substantially to its pathogenesis. In early-onset psoriasis (beginning before age 40 years), carriage of HLA-Cw6 and environmental triggers, such as beta-haemolytic streptococcal infections, are major determinants of disease expression. Moreover, at least nine chromosomal psoriasis susceptibility loci have been identified. Several clinical phenotypes of psoriasis are recognised, with chronic plaque (psoriasis vulgaris) accounting for 90% of cases. Comorbidities of psoriasis are attracting interest, and include impairment of quality of life and associated depressive illness, cardiovascular disease, and a seronegative arthritis known as psoriatic arthritis. A more complete understanding of underlying pathomechanisms is leading to new treatments, which will be discussed in the second part of this Series.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Development, cytokine profile and function of human interleukin 17-producing helper T cells.

            T(H)-17 cells are a distinct lineage of proinflammatory T helper cells that are essential for autoimmune disease. In mice, commitment to the T(H)-17 lineage is dependent on transforming growth factor-beta and interleukin 6 (IL-6). Here we demonstrate that IL-23 and IL-1beta induced the development of human T(H)-17 cells expressing IL-17A, IL-17F, IL-22, IL-26, interferon-gamma, the chemokine CCL20 and transcription factor RORgammat. In situ, T(H)-17 cells were identified by expression of the IL-23 receptor and the memory T cell marker CD45RO. Psoriatic skin lesions contained IL-23-producing dendritic cells and were enriched in the cytokines produced by human T(H)-17 cells that promote the production of antimicrobial peptides in human keratinocytes. Our data collectively indicate that human and mouse T(H)-17 cells require distinct factors during differentiation and that human T(H)-17 cells may regulate innate immunity in epithelial cells.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              A note on exact tests of Hardy-Weinberg equilibrium.

              Deviations from Hardy-Weinberg equilibrium (HWE) can indicate inbreeding, population stratification, and even problems in genotyping. In samples of affected individuals, these deviations can also provide evidence for association. Tests of HWE are commonly performed using a simple chi2 goodness-of-fit test. We show that this chi2 test can have inflated type I error rates, even in relatively large samples (e.g., samples of 1,000 individuals that include approximately 100 copies of the minor allele). On the basis of previous work, we describe exact tests of HWE together with efficient computational methods for their implementation. Our methods adequately control type I error in large and small samples and are computationally efficient. They have been implemented in freely available code that will be useful for quality assessment of genotype data and for the detection of genetic association or population stratification in very large data sets.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2008
                18 June 2008
                : 3
                : 6
                : e2448
                Affiliations
                [1 ]Inserm, U823, Centre de Recherche Albert Bonniot, Epidémiologie des cancers et des affections graves, La Tronche, France
                [2 ]Univ Joseph Fourier, Grenoble, France
                [3 ]INSERM, U794, Fondation Jean Dausset/CEPH, Paris, France
                [4 ]Univ Evry, Evry, France
                [5 ]INSERM, U535, Villejuif, France
                [6 ]Univ Paris-Sud, IFR69, Villejuif, France
                [7 ]CHU Grenoble, Pédiatrie, Grenoble, France
                [8 ]Inserm, U780, Epidemiology and Biostatistics, Villejuif, France
                The University of Queensland, Australia
                Author notes

                Conceived and designed the experiments: FD FK IP. Performed the experiments: FK. Analyzed the data: FD FK VS EB MD. Contributed reagents/materials/analysis tools: FK. Wrote the paper: FD FK VS EB MD IP.

                Article
                08-PONE-RA-04225
                10.1371/journal.pone.0002448
                2413006
                18560587
                ae70976f-339c-4955-b549-6181dc8ec099
                Siroux et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 4 April 2008
                : 26 April 2008
                Page count
                Pages: 6
                Categories
                Research Article
                Genetics and Genomics/Genetics of Disease
                Dermatology/Psoriasis and Other Inflammatory Diseases

                Uncategorized
                Uncategorized

                Comments

                Comment on this article