Effect of BMPR-2 Gene Mutations on Hemodynamic Response by Iloprost Inhalation in Pulmonary Arterial Hypertension
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension
Study type: Observational

Summary: 
      In the present study, the investigators want to investigate the prevalence of BMPR-2 gene
      mutations in the Korean PAH patients (Step-I) and to test that the PAH patients treated with
      iloprost inhalation solution (Ventavis®) would show hemodynamic response, especially assessed
      by exercise echocardiography (Step-II).
    

Detailed description: 
      Pulmonary arterial hypertension (PAH) consists of a group of vascular abnormalities with
      elevated pulmonary arterial pressure and pulmonary vascular resistance. Idiopathic or
      familial PAH is progressive over several years and believed to be fatal without treatment.
      (1-2) The results of the Endothelin Antagonist tRial in mildly symptomatic PAH (EARLY)
      indicate that early diagnosis and treatment of PAH might improve time to clinical worsening
      and emphasize that PAH needs to be diagnosed and treated in the early stages. (3) Germline
      mutations of bone morphogenetic protein receptor (BMPR)-2, a member of the transforming
      growth factor (TGF)-β superfamily, have been found in familial and sporadic forms of
      idiopathic PAH,(4-6) and in appetite-suppressant PAH.(7) The BMPR-2 gene, on chromosome 2q33,
      has 13 exons. Exons 1-3 encode an extracellular domain, exon 4 encodes the transmembrane
      domain, exons 5-11 a serine/threonine kinase domain, and exons 12 and 13 a very large
      intracellular C-terminus of unknown function that appears to be unique to BMPR-2. (8)
      Mutations in familial PAH have been reported in all exons except for 5 and 13. (9) About
      10-25% of sporadic cases of idiopathic PAH are thought to have BMPR-2 mutations (10) and rare
      cases of PAH associated with congenital heart disease, connective tissue disease and drug
      induced PAH were reported. (11-12) It is likely that genetic predispositions exist based on
      normal variations in genes that may influence the pulmonary circulation. However, the studies
      regarding prevalence of BMPR-2 gene mutations in Korean patients have not been performed.

      In a previous study, family members of familial PAH patients showed an increased pulmonary
      artery systolic pressure (PASP) rise during exercise as assessed by echocardiography. (13-14)
      In other study, relatives of idiopathic/familial PAH patients displayed enhanced frequency of
      pulmonary hypertensive response during exercise and that this response is associated with
      mutations in the BMPR-2 gene. (15) These results suggest that asymptomatic gene carriers, in
      the absence of manifest pulmonary hypertension, might have enhanced PASP during exercise and
      more risk to develop resting pulmonary hypertension in the future compared with patients
      without gene mutations. Therefore, the treatment response by variable vasodilators (ex.
      calcium channel blockers, endothelin antagonist or prostacyclin analogues..) may be different
      based on the presence of BMPR-2 gene. In the present study, we want to investigate the
      prevalence of BMPR-2 gene mutations in the Korean PAH patients(Step-I) and to test that the
      PAH patients treated with iloprost inhalation solution (Ventavis®) would show hemodynamic
      response, especially assessed by exercise echocardiography (Step-II).
    

Intervention name(s): Iloprost
Intervention type(s): Drug
Intervention description(s): Iloprost inhalation, 2.5 - 5mcg, 6 times per day
Other intervention name(s): Allowable patients from Step-I; Step-II: Illoprost and Exercise Echo
Intervention MeSH terms: Iloprost
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Previously diagnosed PAH
      
Biospecimen description: 
      BMPR-2 genes
    
Keywords: Pulmonary hypertension; genes; mutation; drug therapy