Genetic and Environmental Characteristics of Primary Pulmonary Hypertension
| Status: | Completed |
|---|---|
| Conditions: | High Blood Pressure (Hypertension), Pulmonary |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | Any - 100 |
| Updated: | 4/21/2016 |
| Start Date: | August 2003 |
| End Date: | July 2009 |
Genetic and Environmental Pathogenesis of PPH
The goal of this study is to identify the modifying genes and environmental features that
regulate the clinical expression of mutations in bone morphogenetic protein receptor 2
(BMPR2); to develop the understanding of how BMPR2 mutations result in disease; and to
identify the undiscovered genetic mutations that cause primary pulmonary hypertension (PPH).
regulate the clinical expression of mutations in bone morphogenetic protein receptor 2
(BMPR2); to develop the understanding of how BMPR2 mutations result in disease; and to
identify the undiscovered genetic mutations that cause primary pulmonary hypertension (PPH).
BACKGROUND:
PPH is a progressive disease that causes obstruction of the smallest arteries in the lungs,
which often leads to heart failure. It threatens the lives of thousands of individuals. PPH
affects both genders at any age, although females are affected twice as often as males. In a
recent important advance, mutations in BMPR2 were associated with both familial and sporadic
PPH. Because only 20% of people with a BMPR2 mutation ever develop PPH, other genes or
modifying biologic events must contribute to the clinical development of the disease. PPH
was recently renamed Idiopathic Pulmonary Arterial Hypertension or Familial Pulmonary
Arterial Hypertension.
DESIGN NARRATIVE:
This study will utilize a database and specimen bank developed from 100 families affected by
PPH across the United States. In families with genetic mutations not yet identified, changes
in the BMPR2 gene will be studied, including in the promoter and intronic regions, and
chance recombination events that could confirm another locus near 2q33 will be examined. New
methods will look for modifier genes in large families with known mutations; examine
kindreds for mitochondrial DNA haplotypes; and test candidate genes, including NOS-1, NOS-3,
and the serotonin transporter. This study will determine the functional mechanisms by which
variations found in the BMPR2 alleles alter BMP signal transduction by defining the
biochemical effects of the mutant proteins on signaling pathways. In addition, the study
will examine the perceived risks and benefits of clinical genetic testing and counseling in
individuals from families at high risk for PPH and will determine how this new information
might be most helpful to these individuals and their families.
PPH is a progressive disease that causes obstruction of the smallest arteries in the lungs,
which often leads to heart failure. It threatens the lives of thousands of individuals. PPH
affects both genders at any age, although females are affected twice as often as males. In a
recent important advance, mutations in BMPR2 were associated with both familial and sporadic
PPH. Because only 20% of people with a BMPR2 mutation ever develop PPH, other genes or
modifying biologic events must contribute to the clinical development of the disease. PPH
was recently renamed Idiopathic Pulmonary Arterial Hypertension or Familial Pulmonary
Arterial Hypertension.
DESIGN NARRATIVE:
This study will utilize a database and specimen bank developed from 100 families affected by
PPH across the United States. In families with genetic mutations not yet identified, changes
in the BMPR2 gene will be studied, including in the promoter and intronic regions, and
chance recombination events that could confirm another locus near 2q33 will be examined. New
methods will look for modifier genes in large families with known mutations; examine
kindreds for mitochondrial DNA haplotypes; and test candidate genes, including NOS-1, NOS-3,
and the serotonin transporter. This study will determine the functional mechanisms by which
variations found in the BMPR2 alleles alter BMP signal transduction by defining the
biochemical effects of the mutant proteins on signaling pathways. In addition, the study
will examine the perceived risks and benefits of clinical genetic testing and counseling in
individuals from families at high risk for PPH and will determine how this new information
might be most helpful to these individuals and their families.
Inclusion Criteria:
- Diagnosis of PPH, or family members of individuals diagnosed with PPH, for inclusion
in the database and specimen bank
We found this trial at
1
site
1211 Medical Center Dr
Nashville, Tennessee 37232
Nashville, Tennessee 37232
(615) 322-5000
Vanderbilt Univ Med Ctr Vanderbilt University Medical Center (VUMC) is a comprehensive healthcare facility dedicated...
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