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Vasoreactivity Tests and TGF-B type II Receptor Gene Mutations

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Conference: 2006 International PHA Conference and Scientific Sessions

Release Date: 06.23.2006

Presentation Type: Abstracts

Eric W. Glissmeyer, BS 1, Gregory T. Havlena, BS 1,2, John Carlquist, PhD 1, Jason T. McKinney, MS 6, Stuart Rich, MD 5, Michael D. McGoon, MD 4, Mary Beth Scholand, MD 1, Miryoung Kim, BS 1, Robert L. Jensen, PhD1, Jon W. Schmidt 1, Kenneth Ward, MD 3, C. Gregory Elliott, MD 1

1. LDS Hospital and the University of Utah School of Medicine, Salt Lake City, Utah
2. Johns Hopkins University School of Medicine, Baltimore, Maryland
3. University of Hawaii, Honolulu, Hawaii
4. Mayo Clinic College of Medicine, Rochester, Minnesota
5. University of Chicago, Chicago, Illinois
6. Idaho Technology, Inc., Salt Lake City, Utah

BACKGROUNDVasoreactivity tests are fundamental to evaluate pulmonary arterial hypertension. Mutations of the TGF-β type II receptor gene, BMPR2, predispose the development of pulmonary hypertension. Previous investigations have not examined the relationship of BMPR2 mutations and vasoreactivity tests.

METHODSWe identified 137 consecutive patients with either idiopathic or familial pulmonary arterial hypertension. Sixty-six patients were excluded because we lacked either DNA samples (n=18) or complete data from a vasoreactivity test (n=48). The remaining 71 patients were screened for BMPR2 cDNA sequence variations and specific variations were confirmed by gene sequencing. The vasoreactivity of patients with nonsynonymousBMPR2 variations (which cause an amino acid change in the protein receptor) was compared to that of patients without nonsynonymous BMPR2 variations.

RESULTSWe found nonsynonymous BMPR2 variations in 29 of 71 patients with idiopathic (n = 16 of 52) or familial (n = 13 of 19) pulmonary arterial hypertension. The rate of vasoreactivity was 3.4 percent in patients with nonsynonymous BMPR2 variations and 33.3 percent in patients without nonsynonymous BMPR2 variations (p =.003). Five of the 29 nonsynonymous variations occur commonly in healthy individuals. None of the remaining 24 patients with nonsynonymous BMPR2 variations demonstrated vasoreactivity and the analysis remained unchanged when we assumed that nonsynonymous variations were present in all 19 patients with familial pulmonary arterial hypertension.

CONCLUSIONPatients with familial or idiopathic pulmonary arterial hypertension and nonsynonymous BMPR2variations are unlikely to demonstrate vasoreactivity. Further trials are required to determine whether chronic therapy can be directed by tests for BMPR2 variations.

Presented previously at the American Thoracic Society International Conference, San Diego, CA, May 22, 2005 thematic poster session.