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IL13RA2 Gene Polymorphisms Are Associated with Systemic Sclerosis
BRIGITTE GRANEL, YANNICK ALLANORE, CHRISTOPHE CHEVILLARD, VIOLAINE ARNAUD, SANDRINE MARQUET, PIERRE-JEAN WEILLER, JEAN-MARC DURAND, JEAN-ROBERT HARLÉ, CLAIRE GRANGE, YVES FRANCES, PHILIPPE BERBIS, JEAN GAUDART, PHILIPPE de MICCO, ANDRÉ KAHAN, and ALAIN DESSEIN ABSTRACT. Objective. To investigate the influence of genetic variability on the phenotypic expression of systemic sclerosis (SSc), by testing possible associations between single nucleotide polymorphisms (SNP) in IL13RA1 and IL13RA2 genes and SSc in a Caucasian population. Methods. As IL13RA1 and IL13RA2 are located on the X chromosome and SSc occurs far more frequently in women than in men, only women were genotyped. The study group comprised 97 women with SSc, 36 with diffuse (dcSSc) and 61 with limited (lcSSc) cutaneous forms of disease, and 109 healthy controls. Patients and controls were Caucasian. We investigated 4 SNP in IL13RA1 and 3 in IL13RA2 by polymerase chain reaction amplifications and enzymatic digestion or primer extension reactions and denaturing high-performance liquid chromatography. Results. We detected an association between IL13RA2 rs638376 and patients with SSc [p = 0.004, odds ratio (OR) = 1.85, confidence interval (CI) 1.22–2.74, p corr = 0.02], as well as with dcSSc in that subgroup of patients (p = 0.01, OR 2.22, 95% CI 1.27–3.89, p corr = 0.05). The IL13RA2 rs638376G allele frequency was higher in patients with SSc (51.6%) than in controls (36.4%, p = 0.003, OR 1.86, 95% CI 1.24–2.79, p corr = 0.015) and in the subgroup with dcSSc (57.6%) than in controls (36.4%, p = 0.003, OR 2.37, 95% CI 1.35–4.15, p corr = 0.015). One other IL13RA2 SNP was only associated with the dcSSc subgroup: the IL13RA2 rs5946040G allele was more common in patients with dcSSc (33.8%) than in controls (17%, p = 0.004, OR 2.5, 95% CI 1.36–4.60, p corr = 0.02). Conclusion. Our data suggest that IL13RA2 gene polymorphisms may be involved in susceptibility to SSc. Further studies are under way to show that they contribute to disease. (First Release Sept 15 2006; J Rheumatol 2006;33:2015-9) Key Indexing Terms:
SYSTEMIC SCLEROSIS From Laboratoire d'Immunologie et de Génétique des Maladies Parasitaires and Equipe Bio-Mathématiques et Informatique Médicale LIF, Université de la Méditerranée - Faculté de Médecine; Service de Médecine Interne and Service de Dermatologie, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille (APHM); Service de Médecine Interne, Hôpital de La Timone; Service de Médecine Interne, Hôpital de La Conception, AP-HM; Site Marseille, EFS-Alpes-Méditerranée, Marseille; Service de Rhumatologie A, Université Paris Descartes, Faculté de Médecine, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris; and Service de Médecine Interne, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France. Supported by INSERM, by the Association des Sclérodermiques de France (ASF) – Groupe Français de Recherche sur la Sclérodermie (GFRS), and by the Assistance Publique-Hôpitaux de Marseille (AORC 2004). B. Granel, MD, Laboratoire d'Immunologie et de Génétique des Maladies Parasitaires, INSERM U399, Université de la Méditerranée - Faculté de Médecine and Service de Médecine Interne, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille (APHM); C. Chevillard, PhD; V. Arnaud, PhD Student; S. Marquet, PhD; A. Dessein, MD, Laboratoire d'Immunologie et de Génétique des Maladies Parasitaires, Université de la Méditerranée - Faculté de Médecine; Y. Frances, MD, INSERM U781, Hôpital Necker, Paris, Service de Médecine Interne, Hôpital Nord, APHM; Y. Allanore, MD, PhD; A. Kahan, MD, PhD, Service de Rhumatologie A, Université Paris Descartes, Faculté de Médecine, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris; P-J. Weiller, MD, Service de Médecine Interne, Hôpital de La Timone; J-M. Durand, MD; J-R. Harlé, MD, Service de Médecine Interne, Hôpital de La Conception; C. Grange, MD, Service de Médecine Interne, Centre Hospitalier Lyon-Sud; P. Berbis, MD, Service de Dermatologie, Hôpital Nord, AP-HM; J. Gaudart, MD, Equipe Bio-Mathématiques et Informatique Médicale LIF, Université de la Méditerranée - Faculté de Médecine; P. de Micco, MD, Site Marseille, EFS-Alpes-Méditerranée. Address reprint requests to Dr. B. Granel, Laboratoire d'Immunologie et de Génétique des Maladies Parasitaires, UMR 399 INSERM, Université de la Méditerranée - Faculté de Médecine de La Timone, 27 boulevard Jean Moulin, 13385 Marseille Cedex 05, France. E-mail: brigitte.granel@medecine.univ-mrs.fr Accepted for publication May 1, 2006.
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