Linked Life Data

15194176

Source:http://linkedlifedata.com/resource/pubmed/id/15194176

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12 Suppl S
pubmed:dateCreated
2004-6-14
pubmed:abstractText
Mutations in two receptors of the transforming growth factor-beta family have recently been shown to be present in the majority of cases of inherited (familial) pulmonary arterial hypertension (PAH). Study of the biology of these receptors, bone morphogenetic protein receptor type-2 (BMPR2), and activin-like kinase type-1 (ALK-1) will certainly reveal pathogenic mechanisms of disease. Exonic mutations in BMPR2 are found in about 50% of patients with familial PAH, and ALK1 mutations are found in a minority of patients with hereditary hemorrhagic telangiectasia and co-existent PAH. Because familial PAH is highly linked to chromosome 2q33, it is likely that the remaining 50% of family cases without exonic mutations have either intronic BMPR2 abnormalities or alterations in the promoter or regulatory genes. Also, only about 10% of patients with "sporadic" idiopathic PAH have identifiable BMPR2 mutations. Mutations in BMPR2 confer a 15% to 20% chance of developing PAH in a carrier's lifetime. Thus, there must be gene-gene or gene-environment interactions that either enhance or prevent the development of the vascular disease in persons carrying a mutation, and there must be other patterns of susceptibility based on genetic makeup. To elucidate the genetic basis of PAH further, investigations are needed, including genome scanning for major and minor genes, analysis of genetic profiles of patients for candidate genes likely to modify risk for disease (e.g., serotonin transporter alleles, nitric oxide-synthases), proteomics, transgenic mice, and altered signal transduction. Advances in genetic testing, presymptomatic screening, and biomarkers should permit early detection of disease in those at risk of PAH and allow trials of preventive therapy in carriers.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0735-1097
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
33S-39S
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Genetic basis of pulmonary arterial hypertension: current understanding and future directions.
pubmed:affiliation
Vanderbilt University School of Medicine, Nashville, Tennessee, United Kingdom. John.Newman@med.va.gov
pubmed:publicationType
Journal Article, Review