The genetics of pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) is a progressive and fatal disease for which there is an ever-expanding body of genetic and related pathophysiological information on disease pathogenesis. Many germline gene mutations have now been described, including mutations in the gene coding bone morphogenic protein receptor type 2 (BMPR2) and related genes. Recent advanced gene-sequencing methods have facilitated the discovery of additional genes with mutations among those with and those without familial forms of PAH (CAV1, KCNK3, EIF2AK4). The reduced penetrance, variable expressivity, and female predominance of PAH suggest that genetic, genomic, and other factors modify disease expression. These multi-faceted variations are an active area of investigation in the field, including but not limited to common genetic variants and epigenetic processes, and may provide novel opportunities for pharmacological intervention in the near future. They also highlight the need for a systems-oriented multi-level approach to incorporate the multitude of biological variations now associated with PAH. Ultimately, an in-depth understanding of the genetic factors relevant to PAH provides the opportunity for improved patient and family counseling about this devastating disease.
['Austin|Eric D|ED|', 'Loyd|James E|JE|']
D000483:Alleles D000818:Animals D052006:Bone Morphogenetic Protein Receptors, Type II D051242:Caveolin 1 D044127:Epigenesis, Genetic D065627:Familial Primary Pulmonary Hypertension D005820:Genetic Testing D012739:Gonadal Steroid Hormones D006801:Humans D006976:Hypertension, Pulmonary D009154:Mutation D009419:Nerve Tissue Proteins D024683:Potassium Channels, Tandem Pore Domain D011498:Protein Precursors D017346:Protein Serine-Threonine Kinases
genetics pulmonary hypertension bone morphogenetic protein receptor, type II