Brief Report: A Regulatory Variant in CCR6 Is Associated With Susceptibility to Antitopoisomerase‐Positive Systemic Sclerosis. Issue 12 (December 2013)

• Record Type: Journal Article
• Authors: Koumakis, Eugénie; Bouaziz, Matthieu; Dieudé, Philippe; Ruiz, Barbara; Riemekasten, Gabriella; Airo, Paolo; Müller‐Nurasyid, Martina; Cusi, Daniele; Matucci‐Cerinic, Marco; Melchers, Inga; Salvi, Erika; Strauch, Konstantin; Peters, Annette; Cuomo, Giovanna; Hachulla, Eric; Diot, Elisabeth; Hunzelmann, Nicolas; Caramaschi, Paola; Riccieri, Valeria; Distler, Jörg H. W.; Tarner, Ingo; Avouac, Jérôme; Letenneur, Luc; Amouyel, Philippe; Lambert, Jean‐Charles; Chiocchia, Gilles; Boileau, Catherine; Allanore, Yannick
• Is Part Of: Arthritis and rheumatism. Volume 65:Issue 12(2013:Dec.)
• Page Start: 3202
• Page End: 3208
• Publication Date: 2013-12
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; Arthritis -- Periodicals; Rheumatic Diseases -- Periodicals; Rhumatisme -- Périodiques; Arthrite -- Périodiques; 616.72
• DOI: 10.1002/art.38136
• Languages: English
• ISSNs: 0004-3591

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="art38136-sec-0001" sec-type="section"> <title>Objective</title> <p>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 <italic>CCR6</italic> gene, a surface marker for Th17 cells, and the causal variant was recently identified. The present study was thus undertaken to investigate whether <italic>CCR6</italic> polymorphisms could also be associated with susceptibility to SSc.</p> </sec> <sec id="art38136-sec-0002" sec-type="section"> <title>Methods</title> <p>Twelve tag single‐nucleotide polymorphisms (SNPs) of <italic>CCR6</italic>, 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 <italic>CCR6</italic> polymorphisms and susceptibility to SSc or its main subtypes. Direct sequencing of DNA was performed to ascertain whether the functional dinucleotide polymorphism of <italic>CCR6</italic> previously identified in RA (<italic>CCR6DNP</italic>) was also present in SSc.</p> </sec> <sec id="art38136-sec-0003" sec-type="section"> <title>Results</title> <p>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 <italic>P</italic> [<italic>P</italic><sub>adj</sub>] = 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, <italic>P</italic><sub>adj</sub> = 1.5 × 10<sup>−3</sup> and OR 1.32, 95% CI 1.17–1.48, <italic>P</italic><sub>adj</sub> = 9.0 × 10<sup>−5</sup>, respectively, relative to healthy controls). Direct sequencing of the DNA of 78 individuals supported the hypothesis that the regulatory dinucleotide <italic>CCR6DNP</italic> could be the causal variant in SSc.</p> </sec> <sec id="art38136-sec-0004" sec-type="section"> <title>Conclusion</title> <p>The results of this study establish <italic>CCR6</italic> 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.</p> </sec> </abstract>