Pulmonary arterial hypertension-new concepts of the genetics of the disease.
- II. interní klinika, Všeobecná fakultní nemocnice a 1. lékařská fakulta Univerzity Karlovy, Praha, Česká republika
Pulmonary arterial hypertension (PAH) has multifactorial pathophysiology with endothelial dysfunction, vasoconstriction, pulmonary vessel wall remodeling and plexiform lesions contributing to increased pulmonary vascular resistance. Recent studies have shown the importance of several mediators in PAH pathophysiology, including prostacyclin, nitric oxide, serotonin, endothelin-1, several cytokines, chemokines, as well as members of the transforming growth factor-$ family (TGF-$). Mutations in two receptors of TGF-$ have been shown to be present in most of the cases of familial PAH, namely bone morphogenetic receptor type-2 (BMPR2) and activin-like kinase-1 (ALK-1). Exogenous mutations were found in at least 50% of patients with familial PAH, the remaining 50% of family cases without exonic mutations have either intronic BMPR2 abnormalities, or alterations in the promoter or regulatory genes. In patients with sporadic (idiopathic) PAH, only 10% have identifiable BMPR2 mutations. The gene-gene or gene-environment interactions therefore play an important role in the development or prevention of PAH in persons carrying a mutation. Advances in genetic testing should allow early presymptomatic screening of patients for early detection of the disease in those at risk for PAH.
Keywords: Pulmonary arterial hypertension; Etiology; Genetics
Published: March 1, 2005 Show citation