Genome-wide association analysis identifies a susceptibility locus for pulmonary arterial hypertension.
Genome-wide association analysis identifies a susceptibility locus for pulmonary arterial hypertension.
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DOI：
10.1038/ng.2581
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发表时间：
2013-05
期刊：
影响因子：
30.8
通讯作者：
Soubrier, Florent
中科院分区：
文献类型：
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作者：
Germain, Marine;Eyries, Melanie;Montani, David;Poirier, Odette;Girerd, Barbara;Dorfmueller, Peter;Coulet, Florence;Nadaud, Sophie;Maugenre, Svetlana;Guignabert, Christophe;Carpentier, Wassila;Vonk-Noordegraaf, Anton;Levy, Marilyne;Chaouat, Ari;Lambert, Jean-Charles;Bertrand, Marion;Dupuy, Anne-Marie;Letenneur, Luc;Lathrop, Mark;Amouyel, Philippe;de Ravel, Thomy J. L.;Delcroix, Marion;Austin, Eric D.;Robbins, Ivan M.;Hemnes, Anna R.;Loyd, James E.;Berman-Rosenzweig, Erika;Barst, Robyn J.;Chung, Wendy K.;Simonneau, Gerald;Tregouet, David A.;Humbert, Marc;Soubrier, Florent
肺动脉高压(PAH)是一种罕见的破坏性疾病，由血管细胞增殖导致小口径肺动脉的进行性闭塞而导致心力衰竭，未经治疗的患者平均生存时间不到三年。PAH可使其他病理情况复杂化，或可发生在导致遗传性PAH的基因突变的背景下，或可被认为是特发性(IPAH)，约占所有PAH的40%。在家族性PAH(FPAH)中，约70%的家族性PAH(FPAH)中发现了低外显性显性BMPR2突变，在约15%的IPAH中发现了BMPR2突变，这些突变被认为是可遗传的PAH。我们基于两项独立的病例对照研究，对625名患者和1,525名健康个体进行了全基因组关联研究，以确定在没有BMPR2突变的情况下与IPAH和fPAH(I/fPAH)相关的新的遗传因素。在定位于18q22.3的CBLN2基因座上发现了全基因组显著的关联，该风险等位基因与I/FPAH的优势比为1.97[1.59~2.45](P=7.47x10−10)。CBLN2在肺中表达，尤其在肺血管内皮细胞中表达，在PAH患者移植肺和移植肺培养的内皮细胞中表达增加。
Pulmonary arterial hypertension (PAH) is a rare and devastating disease, resulting from progressive obliteration of small caliber pulmonary arteries by proliferating vascular cells, and leading to cardiac failure, with an untreated mean survival of less than three years . PAH can complicate other pathological conditions, or can occur in the context of genetic mutations causing heritable PAH, or can be considered as idiopathic (iPAH), which represents approximately 40% of all PAH . Low penetrance dominant BMPR2 mutations are found in ~70% of familial PAH (fPAH), and in ~15% of iPAH which are thereafter considered as heritable PAH . We conducted a Genome-Wide Association Study (GWAS) based on two independent case-control studies for iPAH and fPAH (without BMPR2 mutations) totaling 625 patients and 1,525 healthy individuals, to identify novel genetic factors associated with iPAH and fPAH (i/fPAH) in the absence of BMPR2 mutations. A genome wide significant association was detected at the CBLN2 locus mapping to 18q22.3, the risk allele being associated with an odds ratio for i/fPAH of 1.97 [1.59 – 2.45] (P = 7.47 x 10−10). CBLN2 is expressed in the lung, particularly in pulmonary vascular endothelial cells, and its expression is increased in explanted lungs from PAH patients and in endothelial cells cultured from explanted PAH lungs.
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影响因子：
3.5
作者：
Eyries, M.;Coulet, F.;Soubrier, F.
通讯作者：
Soubrier, F.
影响因子：
4.5
作者：
Allanore Y;Saad M;Dieudé P;Avouac J;Distler JH;Amouyel P;Matucci-Cerinic M;Riemekasten G;Airo P;Melchers I;Hachulla E;Cusi D;Wichmann HE;Wipff J;Lambert JC;Hunzelmann N;Tiev K;Caramaschi P;Diot E;Kowal-Bielecka O;Valentini G;Mouthon L;Czirják L;Damjanov N;Salvi E;Conti C;Müller M;Müller-Ladner U;Riccieri V;Ruiz B;Cracowski JL;Letenneur L;Dupuy AM;Meyer O;Kahan A;Munnich A;Boileau C;Martinez M
通讯作者：
Martinez M
DOI：
10.1073/pnas.0809510106
发表时间：
2009-12-08
影响因子：
11.1
作者：
Bottos, Alessia;Destro, Erika;Arese, Marco
通讯作者：
Arese, Marco
DOI：
10.1165/rcmb.2010-0317oc
发表时间：
2011-08-01
影响因子：
6.4
作者：
Ly Tu;Dewachter, Laurence;Guignabert, Christophe
通讯作者：
Guignabert, Christophe
影响因子：
30.8
作者：
通讯作者：
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