by Phyllis Hanlon, Contributing Writer 

Genes act as information centers within each cell in the body, providing a personal and unique blueprint for every individual. They inform your hair and eye color, body type or shape and other characteristics. Genes are also responsible for diseases that are inherited from parents.

For some individuals with pulmonary arterial hypertension (PAH), one particular gene is of great concern. Changes in a gene that produces a specific protein on the surface of cells called the bone morphogenetic protein receptor type II (BMPR2) have been found to be the most common gene currently associated with PAH, according to a study published in The Lancet Respiratory Medicine in February 2016.

Prof. Nicholas Morrell, University of Cambridge, UK, led an international team of researchers who studied whether changes to BMPR2 were associated with PAH severity and several pre-defined outcomes in patients with idiopathic and familial PAH. Out of 1,550 patients analyzed, 448 (29 percent) had a mutated BMPR2 gene. Patients with a BMPR2 mutation were on average younger and had a higher mean pulmonary artery pressure and pulmonary vascular resistance than those without the mutated gene, according to the study authors.

Patients with a BMPR2 mutation also had worse heart function and did not respond to acute vasodilator testing, which can be an important biomarker in PAH. In summary, patients with changes to the BMPR2 gene were younger, had worse disease and had an increased risk of death and/or lung transplantation than those without the mutation, the study authors found.

A family history of PAH appeared to play an important role in whether patients had a BMPR2 mutation. The study found that for patients who did not recall a family history of PAH, 17 percent were found to have a BMPR2 mutation; but in patients with a family history of PAH, 82 percent had an altered BMPR2 gene. The authors pointed out that both males and females with the gene mutation faced the same risk of death and/or lung transplantation.

Prof. Morrell and his research team commented that most diseases that are inherited usually present at an early age, so their findings regarding the BMPR2 gene are consistent with studies of other genetic conditions. They added that these patients could also experience more serious changes in the blood vessels of the lungs that make PAH worse and could lead to faster disease progression.

So why would a physician test a patient for a BMPR2 mutation in the first place? The study authors suggested that discovering whether the patient does or does not have a BMPR2 mutation could help steer decisions on whether to conduct genetic testing in relatives who don’t have PAH, but who might be at risk of developing the disease. Also, knowing if a patient has a mutation can help clinicians better predict the progression of PAH and drive treatment.

Prof. Morrell said, “This international collaborative study provides important information on the frequency and impact of BMPR2 mutations in PAH. Genetic testing for BMPR2 should be considered in patients with idiopathic or familial PAH.”

An editorial penned by Jeremy A. Mazurek, M.D., and Steven M. Kawut, M.D., M.S., applauded the work of Prof. Morrell and his team. Drs. Mazurek and Kawut noted that, since 2000, mutations in the BMPR2 gene have been associated, in various degrees, with PAH in family members of known mutation carriers, as well as in PAH that occurs without a family history. They explained that sharing data across studies on the individual patient level helps to increase knowledge of the disease and ultimately guide clinicians toward better and more effective treatment options.

In addition to genetic testing, which is recommend by professional guidelines, Drs. Mazurek and Kawut encourage patients and relatives with concerns to receive counseling from experienced professionals at specialized centers. Overall, they reported that this study examined the issue of BMPR2 in a “bigger and better way” that was “well executed” and demonstrated that data collected at the individual patient-level from across studies can lead to greater understanding of PAH.

Read more about this study.

Each PH patient is different. It is essential that you talk to your own doctor about what treatment options are best for you. For more information on finding a doctor or an accredited care center, visit PHA encourages you to always ask your PH specialist before pursuing genetic testing.

Note: Steven Kawut, MD, MS, Professor of Medicine and Epidemiology at the Perelman School of Medicine at the University of Pennsylvania, is Director of the Pulmonary Hypertension/Pulmonary Vascular Disease Program at Penn Medicine, a PHA PHCC accredited program. He also serves on the Pulmonary Hypertension Association (PHA)’s Scientific Leadership Council and as Chair of PHA’s PH Care Centers Registry Task ForceJeremy Aryeh Mazurek, MD, is Asssistant Professor of Clinical Medicine, Cardiology, at the Perelman School of Medicine at the University of Pennsylvania and a member of the practice team at the Pulmonary Hypertension/Pulmonary Vascular Disease Program at Penn Medicine.