• Marine Germain, Mélanie Eyries, David Montani, Odette Poirier, Barbara Girerd, Peter Dorfmüller, Florence Coulet, Sophie Nadaud, Svetlana Maugenre, Christophe Guignabert, Wassila Carpentier, Anton Vonk-Noordegraaf, Marilyne Lévy, Ari Chaouat, Jean-Charles Lambert, Marion Bertrand, Anne-Marie Dupuy, Luc Letenneur, Mark Lathrop, Philippe Amouyel, Thomy J L de Ravel, Marion Delcroix, Eric D Austin, Ivan M Robbins, Anna R Hemnes, James E Loyd, Erika Berman-Rosenzweig, Robyn J Barst, Wendy K Chung, Gerald Simonneau, David A Trégouët, Marc Humbert, and Florent Soubrier.
• Unité Mixte de Recherche en Santé (UMRS) 937, Université Pierre & Marie Curie (UPMC) Université Paris 6 and Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.
• Nat. Genet. 2013 May 1; 45 (5): 518-21.

AbstractPulmonary arterial hypertension (PAH) is a rare, severe disease resulting from progressive obliteration of small-caliber pulmonary arteries by proliferating vascular cells. PAH can occur without recognized etiology (idiopathic PAH), be associated with a systemic disease or occur as a heritable form, with BMPR2 mutated in approximately 80% of familial and 15% of idiopathic PAH cases. We conducted a genome-wide association study (GWAS) based on 2 independent case-control studies for idiopathic and familial PAH (without BMPR2 mutations), including a total of 625 cases and 1,525 healthy individuals. We detected a significant association at the CBLN2 locus mapping to 18q22.3, with the risk allele conferring an odds ratio for PAH of 1.97 (1.59-2.45; P = 7.47 × 10(-10)). CBLN2 is expressed in the lung, and its expression is higher in explanted lungs from individuals with PAH and in endothelial cells cultured from explanted PAH lungs.

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