Rheumatology Advance Access originally published online on December 13, 2006
Rheumatology 2007 46(4):622-625; doi:10.1093/rheumatology/kel378
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Association between an endoglin gene polymorphism and systemic sclerosis-related pulmonary arterial hypertension
1René Descartes University, Medical Faculty, Rheumatology A Department, Cochin Hospital, AP-HP, Paris, 2INSERM U781, Necker Hospital, Paris, 3Lille II University, Internal Medecine Department, Claude Huriez Hospital, Lille, 4Louis Pasteur University, Department of Rheumatology, Hautepierre Hospital, Strasbourg, 5Pierre et Marie Curie University, Internal Medecine Department, Saint-Antoine Hospital, AP-HP, Paris, 6Paris 7 University, Rheumatology Department, Bichat Hospital, AP-HP, Paris, 7René Descartes University, Internal Medicine Department, Cochin Hospital, AP-HP, Paris and 8Department of Biochemistry, Hormonology and Molecular Genetics, Ambroise Paré Hospital, AP-HP, U.V.S.Q, Boulogne, France
Correspondence to: Dr Yannick Allanore, Service de Rhumatologie A, Hôpital Cochin, 27 rue du Faubourg St Jacques, 75014 Paris, France. E-mail: yannick.allanore{at}cch.aphp.fr
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Abstract |
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Systemic sclerosis (SSc) is a connective tissue disorder characterized by early generalized microangiopathy with disturbed angiogenesis. Endoglin gene (ENG) encodes a transmembrane glycoprotein which acts as an accessory receptor for the transforming growth factor-ß (TGF-ß) superfamily, and is crucial for maintaining vascular integrity. A 6-base insertion in intron 7 (6bINS) of ENG has been reported to be associated with microvascular disturbance.
Objectives. Our objective was to investigate the relationship between 6bINS and the vascular complication pulmonary arterial hypertension (PAH) in SSc in a French Caucasian population.
Methods. Two hundred eighty SSc cases containing 29/280 having PAH diagnosed by catheterism were compared with 140 patients with osteoarthritis. Genotyping was performed by polymerase-chain-reaction-based fluorescence and direct sequencing of genomic DNA.
Results. The polymorphism was in Hardy–Weinberg equilibrium. We observed a significant lower frequency of 6bINS allele in SSc patients with associated PAH compared with controls [10.3 vs 23.9%, P = 0.01; odds ratio (OR) 0.37, 95% confidence interval (CI) 0.15–0.89], and a trend in comparison with SSc patients without PAH (10.3 vs 20.3%, P = 0.05; OR: 0.45, 95% CI: 0.19–1.08). Genotypes carrying allele 6bINS were also less frequent in SSc patients with PAH than in controls (20.7 vs 42.9%, P = 0.02).
Conclusions. Thus the frequency of 6bINS differs between SSc patients with or without PAH, suggesting the implication of ENG in this devastating vascular complication of SSc.
KEY WORDS: Systemic sclerosis, Pulmonary arterial hypertension, Endoglin, Gene, TGF-ß
Submitted 21 July 2006;
revised version accepted 11 October 2006.
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  J. Wipff, J. Avouac, D. Borderie, D. Zerkak, H. Lemarechal, A. Kahan, C. Boileau, and Y. Allanore Disturbed angiogenesis in systemic sclerosis: high levels of soluble endoglin Rheumatology, July 1, 2008; 47(7): 972 - 975. [Abstract] [Full Text] [PDF]
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