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JULIEN WIPFF, GUILLAUME GALLIER, PHILIPPE DIEUDE, JEROME AVOUAC, KIET TIEV, ERIC HACHULLA, BRIGITTE GRANEL, ELISABETH DIOT, JEAN SIBILIA, LUC MOUTHON, OLIVIER MEYER, ANDRE KAHAN, MATHILDE VARRET, CATHERINE BOILEAU, and YANNICK ALLANORE ABSTRACT. Objective. To determine whether angiotensin-converting enzyme (ACE) polymorphisms including I/D and 2 single-nucleotide polymorphisms (SNP) affect susceptibility to systemic sclerosis (SSc) in a large French Caucasian population. Methods. A case-control study was performed in 494 patients with SSc and 280 healthy controls for I/D polymorphism. Two supplementary exonic SNP of ACE gene (rs4309, rs4362) were genotyped in 659 patients with SSc and 511 matched healthy controls. Among the whole SSc population, 453 (67%) patients with SSc had the limited cutaneous subtype, 47 (7%) had precapillary pulmonary arterial hypertension, 209 (32%) had digital ulcers, and 10 (1.5%) had renal crisis. A combined analysis of the available results for ACE I/D genotypes in Caucasians was also performed. Results. There was no association between the 3 polymorphic markers and SSc for allelic and genotype frequencies. No association was observed for the different vascular subsets of the disease. Haplotype analyses did not detect any association. The lack of association for ACE I/D was confirmed by the combined analysis. Conclusion. These results in a large cohort of European Caucasian patients with SSc do not support that the ACE gene is implicated in the pathogenesis of SSc and its vascular damage. (J Rheumatol First Release DEC 15 2008; doi:10.3899/jrheum.080622) Key Indexing Terms: SYSTEMIC SCLEROSIS ANGIOTENSIN-CONVERTING ENZYME POLYMORPHISM From Paris Descartes Université, Rhumatologie A, Hôpital Cochin, AP-HP; INSERM U781, Paris Descartes Université, Hôpital Necker; Paris 7 Université, Rhumatologie, Hôpital Bichat, AP-HP; Pierre et Marie Curie Université, Hôpital Saint-Antoine AP-HP, Paris; Lille II Université, Médecine Interne, Lille; INSERM U399, Faculté De Médecine de La Timone, Marseille; INSERM U618, IFR 135, CHU Bretonneau, Tours; Louis Pasteur Université, Rhumatologie, Hôpital Hautepierre, Strasbourg; Paris Descartes Université, Médecine Interne, Hôpital Cochin, AP-HP, Paris; and Department of Biochemistry, UVSQ, Medical Faculty, A. Paré Hospital, AP-HP, 92100 Boulogne-Billancourt, France. Supported by Association des Sclérodermiques de France, Société Française de Rhumatologie, INSERM, and Agence Nationale pour la Recherche (grant R07094KS) and by Groupe Français de Recherche sur la Sclérodermie. J. Wipff, MD, Paris Descartes Université, Rhumatologie A, Hôpital Cochin, AP-HP and INSERM U781, Paris Descartes Université, Hôpital Necker; G. Gallier, MD, INSERM U781, Paris Descartes Université, Hôpital Necker; P. Dieude, MD, Paris 7 Université, Rhumatologie, Hôpital Bichat, AP-HP; J. Avouac, MD, Paris Descartes Université, Rhumatologie A, Hôpital Cochin and INSERM U781, Paris Descartes Université, Hôpital Necker; K. Tiev, MD, Pierre et Marie Curie Université, Hôpital Saint-Antoine AP-HP; E. Hachulla, MD, PhD, Lille II Université, Médecine Interne; B. Granel, MD, INSERM U399, Faculté De Médecine de La Timone; E. Diot, MD, INSERM U618, IFR 135, CHU Bretonneau; J. Sibilia, MD, Louis Pasteur Université, Rhumatologie, Hôpital Hautepierre; L. Mouthon, MD, PhD, Paris Descartes Université, Médecine Interne, Hôpital Cochin, AP-HP; O. Meyer, MD, PhD, Paris 7 Université, Rhumatologie, Hôpital Bichat, AP-HP; A. Kahan, MD, PhD, Paris Descartes Université, Rhumatologie A, Hôpital Cochin, AP-HP; M. Varret, MD, INSERM U781, Paris Descartes Université, Hôpital Necker; C. Boileau, MD, PhD, INSERM U781, Paris Descartes Université, Hôpital Necker and Department of Biochemistry, UVSQ, Medical Faculty, A. Paré Hospital, AP-HP; Y. Allanore, MD, Paris Descartes Université, Rhumatologie A, Hôpital Cochin, AP-HP and INSERM U781, Paris Descartes Université, Hôpital Necker. Address reprint requests to Dr. 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 September 15, 2008. |
