Absence of influence of gender and BMPR2 mutation type on clinical phenotypes of pulmonary arterial hypertension

Respir Res. 2010 Jun 10;11(1):73. doi: 10.1186/1465-9921-11-73.


Background: Previous studies indicate that patients with pulmonary arterial hypertension (PAH) carrying a mutation in the bone morphogenetic protein receptor type 2 (BMPR2) gene, develop the disease 10 years earlier than non-carriers, and have a more severe hemodynamic compromise at diagnosis. A recent report has suggested that this may only be the case for females and that patients with missense mutations in BMPR2 gene have more severe disease than patients with truncating mutations.

Methods: We reviewed data from all patients with PAH considered as idiopathic and patients with a family history of PAH, who underwent genetic counselling in the French PAH network between January, 1st 2004 and April, 1st 2010. We compared clinical, functional, and hemodynamic characteristics between carriers and non-carriers of a BMPR2 mutation, according to gender or BMPR2 mutation type.

Results: PAH patients carrying a BMPR2 mutation (n = 115) were significantly younger at diagnosis than non-carriers (n = 267) (35.8 +/- 15.4 and 47.5 +/- 16.2 respectively, p < 0.0001). The presence of a BMPR2 mutation was associated with a younger age at diagnosis in females (36.4 +/- 14.9 in BMPR2 mutation carriers and 47.4 +/- 15.8 in non-carriers, p < 0.0001), and males (34.6 +/- 16.8 in BMPR2 mutation carriers and 47.8 +/- 17.1 in non-carriers, p < 0.0001). BMPR2 mutation carriers had a more severe hemodynamic compromise at diagnosis, but this was not influenced by gender. No differences in survival and time to death or lung transplantation were found in male and female PAH patients carrying a BMPR2 mutation. No differences were observed in clinical outcomes according to the type of BMPR2 mutations (missense, truncating, large rearrangement or splice defect).

Conclusion: When compared to non-carriers, BMPR2 mutation carriers from the French PAH network are younger at diagnosis and present with a more severe hemodynamic compromise, irrespective of gender. Moreover, BMPR2 mutation type had no influence on clinical phenotypes in our patient population.

MeSH terms

  • Activin Receptors, Type II / genetics
  • Adult
  • Age Factors
  • Blood Pressure / genetics*
  • Bone Morphogenetic Protein Receptors, Type II / genetics*
  • Female
  • France
  • Genetic Predisposition to Disease
  • Humans
  • Hypertension, Pulmonary / genetics*
  • Hypertension, Pulmonary / mortality
  • Hypertension, Pulmonary / physiopathology
  • Hypertension, Pulmonary / surgery
  • Kaplan-Meier Estimate
  • Lung Transplantation
  • Male
  • Middle Aged
  • Mutation*
  • Phenotype
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Sex Factors
  • Time Factors
  • Young Adult


  • ACVRL1 protein, human
  • Activin Receptors, Type II
  • BMPR2 protein, human
  • Bone Morphogenetic Protein Receptors, Type II