title: Relationship of BMPR2 mutations to vasoreactivity in pulmonary arterial hypertension.
abstract: BACKGROUND
  Vasoreactivity tests are fundamental in evaluating pulmonary arterial hypertension (PAH). Mutations of the transforming growth factor-beta type II receptor gene, BMPR2, predispose to the development of pulmonary hypertension and may alter the response to vasodilators. Previous investigations have not examined the relationship of BMPR2 mutations to vasoreactivity.
  
  
  RESULTS
  We identified 133 consecutive unrelated patients with either idiopathic or familial PAH. Sixty-six patients were excluded because we lacked either DNA samples (n=18) or complete data from a vasoreactivity test (n=48). The remaining 67 patients were screened for BMPR2 DNA sequence variations, and specific variations were confirmed by gene sequencing. The vasoreactivity of patients with nonsynonymous BMPR2 variations was compared with that of patients without nonsynonymous BMPR2 variations. We found nonsynonymous BMPR2 variations in 27 of 67 patients with idiopathic (n=16 of 52) or familial (n=11 of 15) PAH. Vasoreactivity was identified in 3.7% of 27 patients with nonsynonymous BMPR2 variations and in 35% of 40 patients without nonsynonymous BMPR2 variations (P=0.003). Five of the 27 nonsynonymous variations occur commonly in healthy individuals. None of the remaining 22 patients with BMPR2 variations demonstrated vasoreactivity, and the analysis remained unchanged when we assumed that nonsynonymous BMPR2 variations were present in all 15 patients with familial PAH.
  
  
  CONCLUSIONS
  Patients with familial or idiopathic PAH and nonsynonymous BMPR2 variations are unlikely to demonstrate vasoreactivity. Further trials are required to determine whether long-term therapy can be directed by tests for BMPR2 variations.
authors.affiliation: LDS Hospital, University of Utah School of Medicine, Salt Lake City, Utah, USA. ldgellio@ihc.com
authors.forename: C Gregory
authors.initials: CG
authors.lastname: Elliott
authors.forename: Eric W
authors.initials: EW
authors.lastname: Glissmeyer
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Havlena
authors.forename: John
authors.initials: J
authors.lastname: Carlquist
authors.forename: Jason T
authors.initials: JT
authors.lastname: McKinney
authors.forename: Stuart
authors.initials: S
authors.lastname: Rich
authors.forename: Michael D
authors.initials: MD
authors.lastname: McGoon
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Scholand
authors.forename: Miryoung
authors.initials: M
authors.lastname: Kim
authors.forename: Robert L
authors.initials: RL
authors.lastname: Jensen
authors.forename: Jon W
authors.initials: JW
authors.lastname: Schmidt
authors.forename: Kenneth
authors.initials: K
authors.lastname: Ward
mesh_terms: D000293:Adolescent; D000328:Adult; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017422:Sequence Analysis, DNA; D014661:Vasoconstriction / Q000235:genetics; D014664:Vasodilation / Q000235:genetics*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II