title: High Frequency of Pulmonary Hypertension-Causing Gene Mutation in Chinese Patients with Chronic Thromboembolic Pulmonary Hypertension.
abstract: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is unknown. Histopathologic studies revealed that pulmonary vasculature lesions similar to idiopathic pulmonary arterial hypertension (PAH) existed in CTEPH patients as well. It's well-known that genetic predisposition plays an important role in the mechanism of PAH. So we hypothesized that PAH-causing gene mutation might exist in some CTEPH patients and act as a background to facilitate the development of CTEPH. In this study, we analyzed 7 PAH-causing genes including BMPR2, ACVRL1, ENG, SMAD9, CAV1, KCNK3, and CBLN2 in 49 CTEPH patients and 17 patients recovered from pulmonary embolism (PE) but without pulmonary hypertension(PH). The results showed that the nonsynonymous mutation rate in CTEPH patients is significantly higher than that in PE without PH patients (25 out of 49 (51%) CTEPH patients vs. 3 out of 17 PE without PH patients (18%); p = 0.022). Four CTEPH patients had the same point mutation in ACVRL1 exon 10 (c.1450C>G), a mutation approved to be associated with PH in a previous study. In addition, we identified two CTEPH associated SNPs (rs3739817 and rs55805125). Our results suggest that PAH-causing gene mutation might play an important role in the development of CTEPH.
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.|Center for Pulmonary Vascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Qunying
authors.initials: Q
authors.lastname: Xi
authors.affiliation: Center for Pulmonary Vascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Center for Pulmonary Vascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Center for Pulmonary Vascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.|Center for Pulmonary Vascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D002681:China; D002908:Chronic Disease; D065627:Familial Primary Pulmonary Hypertension / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D011655:Pulmonary Embolism / Q000235:genetics*; D017422:Sequence Analysis, DNA
references.citation: Nat Genet. 2013 May;45(5):518-21
references.pmid: 23502781
references.citation: Eur Respir J. 2013 Feb;41(2):462-8
references.pmid: 22700839
references.citation: J Am Coll Cardiol. 2013 Dec 24;62(25 Suppl):D13-21
references.pmid: 24355637
references.citation: J Am Coll Cardiol. 2013 Dec 24;62(25 Suppl):D4-12
references.pmid: 24355640
references.citation: Hum Genet. 2014 May;133(5):471-9
references.pmid: 24442418
references.citation: Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 1):1577-86
references.pmid: 11029379
references.citation: N Engl J Med. 2001 Aug 2;345(5):325-34
references.pmid: 11484689
references.citation: Circ Res. 2003 Nov 14;93(10):957-64
references.pmid: 14551239
references.citation: Thorax. 2004 May;59(5):446-8
references.pmid: 15115879
references.citation: N Engl J Med. 2004 May 27;350(22):2257-64
references.pmid: 15163775
references.citation: Circulation. 2004 Sep 14;110(11):1499-506
references.pmid: 15353500
references.citation: Chest. 1993 Mar;103(3):685-92
references.pmid: 8449052
references.citation: Circulation. 1999 Mar 16;99(10):1325-30
references.pmid: 10077516
references.citation: Chest. 2006 Jan;129(1):192-7
references.pmid: 16424432
references.citation: Am J Respir Crit Care Med. 2006 Jun 1;173(11):1270-5
references.pmid: 16514114
references.citation: Chest. 2006 Jul;130(1):172-5
references.pmid: 16840398
references.citation: Hum Mol Genet. 2009 Aug 1;18(15):2791-801
references.pmid: 19419974
references.citation: Am J Respir Crit Care Med. 2010 May 1;181(9):992-6
references.pmid: 20075386
references.citation: Br J Haematol. 2010 May;149(4):478-83
references.pmid: 20331466
references.citation: Circ Cardiovasc Genet. 2012 Jun;5(3):336-43
references.pmid: 22474227
references.citation: Prog Cardiovasc Dis. 2012 Sep-Oct;55(2):134-43
references.pmid: 23009910
references.citation: Eur Respir J. 2013 Jan;41(1):224-32
references.pmid: 22903956
references.citation: N Engl J Med. 2013 Jul 25;369(4):351-61
references.pmid: 23883380