Document Detail

Primary pulmonary hypertension may be a heterogeneous disease with a second locus on chromosome 2q31.
MedLine Citation:
PMID:  12821254     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: The aim of our study was to identify genetic causes of primary pulmonary hypertension (PPH), to estimate the proportion of families with mutations in the BMPR2 (bone morphogenetic protein receptor type 2) gene, and to examine whether genetic heterogeneity might play a role.
BACKGROUND: The BMPR2 mutations have been identified in a substantial portion of patients with familial or sporadic PPH. However, the genetic cause of PPH remains unclear in at least 45% of families.
METHODS: We investigated 130 members of 10 families with at least 1 PPH patient, recruited without selection for familial disease. Manifest PPH was documented in 21 individuals. An increase in pulmonary artery systolic pressure (PASP) above 40 mm Hg during supine bicycle exercise was found in 46 healthy individuals. Their PASP increased from 21.0 +/- 4.6 mm Hg at rest to 54.0 +/- 9.8 mm Hg during exercise. In 51 relatives, PASP values were normal at rest and during exercise, and 12 members were classified as status unknown.
RESULTS: Two families showed a mutation in the BMPR2 gene. Three families with no BMBR2 mutation showed evidence for linkage to a more proximal location on chromosome 2q31 (odds ratio [OR] for linkage 1.1.10(6):1). This locus, designated PPH2, maps in-between the markers D2S335 and D2S2314. We obtained significant support for heterogeneity in PPH with an OR of 2.8.10(11).
CONCLUSIONS: We conclude that PPH may be a genetically heterogeneous disorder with at least two-and possibly more-causative genes.
Matthias Rindermann; Ekkehard Grünig; Albrecht von Hippel; Rolf Koehler; Gabriel Miltenberger-Miltenyi; Derliz Mereles; Karlin Arnold; Michael Pauciulo; William Nichols; Horst Olschewski; Marius M Hoeper; Jörg Winkler; Hugo A Katus; Wolfgang Kübler; Claus R Bartram; Bart Janssen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  41     ISSN:  0735-1097     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-06-24     Completed Date:  2003-07-09     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2237-44     Citation Subset:  AIM; IM    
Institute of Human Genetics, University of Heidelberg, Germany.
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MeSH Terms
Aged, 80 and over
Blood Pressure / physiology
Bone Morphogenetic Protein Receptors, Type II
Chromosomes, Human, Pair 2 / genetics*
Exercise Test
Genetic Heterogeneity*
Genetic Predisposition to Disease / genetics
Hypertension, Pulmonary / etiology*,  genetics*,  physiopathology
Locus Control Region / genetics*
Middle Aged
Mutation / genetics*
Protein-Serine-Threonine Kinases / genetics*
Pulmonary Artery / physiopathology
Reg. No./Substance:
EC Kinases; EC protein, human; EC Morphogenetic Protein Receptors, Type II

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