Researchers Publish The Most Comprehensive Data Ever on PAH Genes

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An international group of scientists has comprehensively characterized the genetics of pulmonary arterial hypertension (PAH). This new information could ultimately help clinicians treat the disease based on individual traits and genetic makeup. This is the most complete set of genetic data that has been collected about the disease to date.

PAH  is a rare condition characterized by high blood pressure of the lung arteries. The disease can be associated with other conditions, such as lung disease and heart disease. Genetics in part determine whether someone develops PAH. Although PAH incidence increases with age, people of any age may develop PAH. PAH can cause heart failure and possible death.

Dr. Rajiv Machado from the University of Lincoln, UK led the research effort to compile the genetic data from hundreds of people with PAH. The work, titled Pulmonary Arterial Hypertension: A Current Perspective on Established and Emerging Molecular Genetic Defects appeared September 21st in the online academic journal Human Mutation. The study was a collaboration between specialist PAH centers in Germany, France, North America and the UK. The scientists performed an analysis of the 10 genes known to cause PAH and compiled of all of known the gene mutations.

Mutations in a gene called BMPR2 are most commonly observed, however other genetic mutations are possible. According to the researchers, “transforming growth factor beta (TGF-β) pathway have been implicated in disease pathogenesis. Specifically, studies have confirmed activin A receptor type II-like 1 (ACVRL1), endoglin (ENG) and members of the SMAD family.”

The new study describes 370 BMPR2 mutations that were either previously excluded or identified since the last comprehensive mutation update by these same researchers that was published in 2009. Of these, 81 are completely novel variations.

Dr. Machado noted: “This is the most comprehensive and complete compilation of all defective variations in the genetic risk factors for PAH. This will allow the clinical geneticists, with a greater degree of certainty, to conclude that the gene variations present in a patient are either disease causing or of unknown significance. This could inform a patient’s decisions about starting a family or undertaking pre-natal testing. Prior to this a clinician would have to try and understand genetic data received for a single patient by trawling through historic manuscripts to make a diagnosis. This report has the potential to be of great importance to the diagnostic centres around the world.

“The continuing identification of genetic factors, as explored in this paper, provides unique insight to the genetic mechanisms driving disorders of pulmonary vascular function. These data provide a key resource in data interpretation and how these genetic insights may lead to the potential discovery and delivery of novel targeted therapeutic options in PAH.”

The information is available on a freely available public data site called ClinVar, and will also be accessible via a page set up by Machado.