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Polymorphic Markers of the Fibrillin-1 Gene and Systemic Sclerosis in European Caucasian Patients JULIEN WIPFF, MATTHIEU GIRAUD, JEAN SIBILIA, LUC MOUTHON, OLIVIER MEYER, KIET TIEV, PAOLO AIRO, PAOLA CARAMASCHI, SERENA GUIDUCCI, HENRI JEAN GARCHON, MARCO MATUCCI-CERINIC, ANDRÉ KAHAN, JÉRÔME AVOUAC, CATHERINE BOILEAU, and YANNICK ALLANORE
ABSTRACT. Methods. We investigated 6 FBN1 polymorphisms in 2 cohorts: one with 399 French subjects (243 SSc patients/156 matched healthy controls), another with 319 Italian subjects (266 SSc patients/153 matched healthy controls). The 6 FBN1 polymorphisms included one single-nucleotide polymorphism (SNP) in intron C to replicate its genetic association and 5 microsatellite markers (D15S1028 in the 5' region, intragenic MTS2 and MTS3, and D15S123 and D15S143 in the 3' region). Then we investigated the French cohort enlarged to 362 SSc patients/162 matched healthy controls for 5 tagging single nucleotide polymorphisms (tagSNP) that account for the common genetic diversity according to HapMap data. We used Arlequin, Cocaphase, Phase 2 software, and Fisher's exact test for statistical analyses. Results. All markers were in Hardy-Weinberg equilibrium. No association was detected between polymorphic markers and disease in either the French or Italian cohorts, even for specific phenotypes. No significant differences between patients and controls were detected for the 5 tagSNP. Conclusion. In contrast with data from Choctaw and Japanese patients, no association was detected between the polymorphic markers of FBN1 and SSc in 2 European Caucasian populations. These discrepancies may be explained by ethnic specificities and heterogeneity associated with this multigenic disease. (J Rheumatol First Release Feb 15 2008) Key Indexing Terms:
SYSTEMIC SCLEROSIS
From the Department of Rheumatology A, Paris Descartes University, Medical Faculty, Cochin Hospital, AP-HP, Paris; INSERM U781, Paris Descartes University, Necker Hospital, Paris; INSERM U580, Paris Descartes University, Necker Hospital, Paris; Department of Rheumatology, Louis Pasteur University, Hautepierre Hospital, Strasbourg; Department of Internal Medicine, Paris Descartes University, Medical Faculty, Cochin Hospital, AP-HP, Paris; Rheumatology Department, Paris VII University, Bichat Hospital, AP-HP, Paris; Department of Internal Medicine, Pierre et Marie Curie University, Medical Faculty, Saint-Antoine Hospital, AP-HP, Paris, France; Rheumatology and Immunology Department, Spedali Civili, Brescia; Department of Clinical and Experimental Medicine, University Hospital, Verona; and University of Florence, Department of Medicine, Section of Rheumatology, Villa Monna Tessa, Florence, Italy. Supported by the Association des Sclérodermiques de France, Société Française de Rhumatologie, and Groupe Français de Recherche sur la Sclérodermie. Dr. Y. Allanore was supported by a bursary from the Servier Institute. J. Wipff, MD; J. Avouac, MD; Y. Allanore, MD, PhD, Department of Rheumatology A, Paris Descartes University, Medical Faculty, Cochin Hospital, AP-HP, INSERM U781, Paris Descartes University, Necker Hospital; M. Giraud, PhD; H-J. Garchon, PhD, INSERM U580, Paris Descartes University, Necker Hospital; J. Sibilia, MD, PhD, Department of Rheumatology, Louis Pasteur University, Hautepierre Hospital; L. Mouthon, MD, PhD, Department of Internal Medicine, Paris Descartes University, Medical Faculty, Cochin Hospital; O. Meyer, MD, PhD, Rheumatology Department, Paris VII University, Bichat Hospital, AP-HP; K. Tiev, MD, Department of Internal Medicine, Pierre et Marie Curie University, Medical Faculty, Saint-Antoine Hospital, AP-HP; P. Airo, MD, Rheumatology and Immunology Department, Spedali Civili; P. Caramaschi, MD, Department of Clinical and Experimental Medicine, University Hospital, Verona; S. Guiducci, MD; M. Matucci-Cerinic, MD, PhD, University of Florence, Department of Medicine, Section of Rheumatology, Villa Monna Tessa, Florence; A. Kahan, MD, PhD, Department of Rheumatology A, Paris Descartes University, Medical Faculty, Cochin Hospital, AP-HP; C. Boileau, PharmD, PhD, INSERM U781, Paris Descartes University, Necker Hospital, Paris. Address reprint requests to Prof. Y. Allanore, Service de Rhumatologie A, Hôpital Cochin, 27 rue du Faubourg St. Jacques, 75014 Paris, France. E-mail: yannick.allanore@cch.aphp.fr Accepted for publication November 23, 2007.
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