A regulatory variant in CCR6 is associated with susceptibility to antitopoisomerase-positive systemic sclerosis

Autor: Koumakis, E., Bouaziz, M., Dieude, P., Ruiz, B., Riemekasten, G., Airo, P., Muller Nurasyid, M., Cusi, D., Matucci Cerinic, M., Melchers, I., Salvi, E., Strauch, K., Peters, A., Cuomo, G., Hachulla, E., Diot, E., Hunzelmann, N., Caramaschi, P., Riccieri, Valeria, Distler, J. H., Tarner, I., Avouac, J., Letenneur, L., Amouyel, P., Lambert, J. C., Chiocchia, G., Boileau, C., Allanore, Y.
Přispěvatelé: Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1152 Statistique et Génome, Institut National de la Recherche Agronomique (INRA), U699, Institut National de la Santé et de la Recherche Médicale (INSERM), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Leibniz Association, Civil Hospital, Ludwig Maximilians University of Munich, Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), University Hospital, Università degli Studi di Milano [Milano] (UNIMI), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), University of Freiburg [Freiburg], Munich Heart Alliance, Munich, Germany, Partenaires INRAE, Helmholtz-Zentrum München (HZM), Università degli studi di Napoli Federico II, Université de Lille, Droit et Santé, University of Cologne, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Justus-Liebig-Universität Gießen (JLU), Kerckhoff clinic, U 897, Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Université Paris Descartes - Paris 5 (UPD5), Hôpital Ambroise Paré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Actelion, Bayer, GlaxoSmithKline, Bristol-Myers Squibb, UCB, Celgene, JB Therapeutics, Boehringer Ingelheim, Novartis, RuiYi, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Statistique et Génome (SG), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Ludwig-Maximilians University [Munich] (LMU), Università degli Studi di Milano = University of Milan (UNIMI), Università degli Studi di Firenze = University of Florence (UniFI), Helmholtz Zentrum München = German Research Center for Environmental Health, University of Naples Federico II = Università degli studi di Napoli Federico II, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Koumakis, E, Bouaziz, M, Dieudé, P, Ruiz, B, Riemekasten, G, Airo, P, Müller Nurasyid, M, Cusi, D, Matucci Cerinic, M, Melchers, I, Salvi, E, Strauch, K, Peters, A, Cuomo, Giovanna, Hachulla, E, Diot, E, Hunzelmann, N, Caramaschi, P, Riccieri, V, Distler, Jh, Tarner, I, Avouac, J, Letenneur, L, Amouyel, P, Lambert, Jc, Chiocchia, G, Boileau, C, Allanore, Y.
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Arthritis and Rheumatism
Arthritis and Rheumatism, Wiley, 2013, 65 (12), pp.3202-3208. ⟨10.1002/art.38136⟩
Arthritis and Rheumatism, 2013, 65 (12), pp.3202-3208. ⟨10.1002/art.38136⟩
ISSN: 0004-3591
1529-0131
Popis: International audience; Objective: Recognition of the well-known pleiotropism of autoimmune genes supports the concept of a shared pathogenesis across autoimmune diseases such as rheumatoid arthritis (RA) and systemic sclerosis (SSc). Studies have reproducibly demonstrated an association between susceptibility to RA and polymorphisms of the CCR6 gene, a surface marker for Th17 cells, and the causal variant was recently identified. The present study was thus undertaken to investigate whether CCR6 polymorphisms could also be associated with susceptibility to SSc. Methods: Twelve tag single-nucleotide polymorphisms (SNPs) of CCR6, including the known RA-associated SNP rs3093023, were genotyped in a total of 2,411 SSc patients and 7,084 healthy individuals from 3 European populations (France, Italy, and Germany). Meta-analyses of the data were performed to assess whether an association exists between CCR6 polymorphisms and susceptibility to SSc or its main subtypes. Direct sequencing of DNA was performed to ascertain whether the functional dinucleotide polymorphism of CCR6 previously identified in RA (CCR6DNP) was also present in SSc. Results: Combined analyses revealed an association between the rs10946216 SNP and SSc susceptibility (odds ratio [OR] 1.13, 95% confidence interval [95% CI] 1.05-1.21, adjusted P [P-adj] = 0.026). The rs3093023 A allele and rs10946216 T allele were in high linkage disequilibrium, and both were found to confer disease susceptibility in the antitopoisomerase-positive subset of SSc patients (OR 1.27, 95% CI 1.13-1.42, P-adj = 1.5 x 10(-3) and OR 1.32, 95% CI 1.17-1.48, P-adj = 9.0 x 10(-5), respectively, relative to healthy controls). Direct sequencing of the DNA of 78 individuals supported the hypothesis that the regulatory dinucleotide CCR6DNP could be the causal variant in SSc. Conclusion: The results of this study establish CCR6 as a new susceptibility factor for antitopoisomerase-positive SSc, as demonstrated in 3 European Caucasian populations, confirming the notion that SSc and RA could conceivably share autoimmune risk alleles. The results also suggest a potential role of the interleukin-17 pathway in SSc.
Databáze: OpenAIRE
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