Relationship of BMPR2 mutations to vasoreactivity in pulmonary arterial hypertension.
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.
Elliott
C Gregory
CG
LDS Hospital, University of Utah School of Medicine, Salt Lake City, Utah, USA. ldgellio@ihc.com
Glissmeyer
Eric W
EW
Havlena
Gregory T
GT
Carlquist
John
J
McKinney
Jason T
JT
Rich
Stuart
S
McGoon
Michael D
MD
Scholand
Mary Beth
MB
Kim
Miryoung
M
Jensen
Robert L
RL
Schmidt
Jon W
JW
Ward
Kenneth
K
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
D014665:Vasodilator Agents; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II