High Frequency of Pulmonary Hypertension-Causing Gene Mutation in Chinese Patients with Chronic Thromboembolic Pulmonary Hypertension

PLoS One. 2016 Jan 28;11(1):e0147396. doi: 10.1371/journal.pone.0147396. eCollection 2016.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • China
  • Chronic Disease
  • Familial Primary Pulmonary Hypertension / genetics*
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Point Mutation
  • Polymorphism, Single Nucleotide
  • Pulmonary Embolism / genetics*
  • Sequence Analysis, DNA

Grant support

This study was supported by a grant from National Key Technology R&D Program in the 12th Five year Plan of China (2011BA11B17). ZHL recieved the funding.