Pulmonary hypertension (PH) is a rare disease characterized by abnormally high blood pressure in the lungs that damages the pulmonary arteries. These vessels, which are responsible for transporting the blood from the heart to the lungs, become narrowed and blocked due to the disease. Therefore, the heart needs to work harder to properly pump the blood, which can result in an enlarged and weaker organ, as well as in heart failure and even death.

Cases of pulmonary hypertension are sometimes associated with an underlying disease, which can be a heart or lung condition, but also blood clots, chronic obstructive pulmonary diseases, such as emphysema, connective tissue disorders, such as scleroderma or lupus, sleep apnea and other sleep disorders, sickle cell anemia, chronic liver disease (cirrhosis) and AIDS. It is also believed that genetics play an important role in the development of the disease as well.

Correlation Between Pulmonary Hypertension and Genetics

Scientific research has demonstrated that mutations in the BMPR2 gene are responsible for the development of pulmonary hypertension. This gene is an important element for the regulation of numerous cells in the tissues. The mutation in the BMPR2 gene promotes cell division, prevents cell death and results in cell overgrowth, which is a cause for the blockage of the vessels and resistance to blood flow. In addition to the BMPMR2 gene, researchers recognize that other genes may be associated with the development of the disease, while environmental factors are also important, even in patients with the mutation.

“Major discoveries have been obtained within the last decade in the field of hereditary predisposition to pulmonary arterial hypertension (PAH). Among them, the identification of bone morphogenetic protein receptor type 2 (BMPR2) as the major predisposing gene and activin A receptor type II-like kinase-1 (ACVRL1, also known as ALK1) as the major gene when PAH is associated with hereditary hemorrhagic telangiectasia. The mutation detection rate for the known genes is approximately 75% in familial PAH, but the mutation shortfall remains unexplained even after careful molecular investigation of these genes,” as explained in the study “Genetics and genomics of pulmonary arterial hypertension.”

Impact Of Genetics In Hereditary Pulmonary Hypertension

According to the National Institutes of Health (NIH)’s Genetics Home Reference, pulmonary hypertension is inherited in an autosomal dominant pattern. This means that every cell has one copy of an altered BMPR2 gene. As the mutation passes down from one generation to other, the disease is known as familial PH, and the next generations will develop it earlier in life, which is called anticipation. However, not every members of a family will receive it and familial PH represents a small share from the total of PH patients.

“The careful study of families and routine genetic diagnosis facilitated natural history studies based on large registries of PAH patients to be set up in different countries. These longitudinal or cross-sectional studies permitted the clinical characterization of PAH in mutation carriers to be accurately described. The availability of molecular genetic diagnosis has opened up a new field for patient care, including genetic counseling for a severe disease, taking into account that the major predisposing gene has a highly variable penetrance between families. Molecular information can be drawn from the genomic study of affected tissues in PAH, in particular, pulmonary vascular tissues and cells, to gain insight into the mechanisms leading to the development of the disease,” added the authors of the study.


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