Genetics May Influence the Body’s Response to Low Oxygen, Pitt Study Finds
University of Pittsburgh Schools of Medicine researchers have made a significant breakthrough in understanding the body’s response to limited oxygen and its impact on blood vessel disease of the lung. By analyzing the genomes of over 20,000 individuals in the U.S., France, England, and Japan and conducting molecular studies in the lab, the research team has identified a shared genetic trait that could predict a higher risk of small lung vessel disease, known as pulmonary hypertension, and its more severe form, pulmonary arterial hypertension. These findings could potentially influence the development of targeted drug therapies to address the body’s response to limited oxygen. The study was recently published in Science Translational Medicine.
Senior author Stephen Chan, M.D., Ph.D., who serves as the Vitalant Chair in Vascular Medicine and director of the Vascular Medicine Institute at Pitt, emphasized the significance of this new knowledge in identifying individuals at a higher genetic risk of pulmonary hypertension. This, in turn, could pave the way for precision medicine practices to offer tailored treatments.
Pulmonary hypertension encompasses a range of conditions that result in high blood pressure in the arteries of the lung and the right side of the heart. The disease is characterized by a decreased supply of oxygen to the lung tissue and the blood, is chronic and deadly, and its molecular origins and genetic background have remained elusive.
The Chan lab utilized a combined approach of genomics and biochemistry to uncover a gene pair that plays a crucial role in regulating blood vessel metabolism and disease. This gene pair consists of a long non-coding RNA molecule, which acts as a messenger facilitating the translation of the body’s genetic code into protein products, and a protein binding partner. Their interaction was found to be frequently active in cells exposed to low oxygen compared to normal cells.
Furthermore, the research team found that a single DNA letter change directing the expression of this RNA-protein pair under low oxygen conditions was associated with a higher genetic risk of pulmonary hypertension across diverse patient populations.
According to Chan, pulmonary hypertension is a challenging disease to study due to its limited number of patients, making it difficult to identify rare genetic variations that still have a significant impact. To address this, Pitt scientists collaborated with researchers globally and utilized public research datasets such as All of Us, a nationwide health registry funded by the National Institutes of Health.
