Genetics may influence the body’s response to lack of oxygen

Researchers at the University of Pittsburgh School of Medicine have discovered a fundamental mechanism that controls the body’s response to oxygen limitation and regulates blood vessel disease in the lungs. The results are published in “Scientific translational medicine.”

By analyzing the genomes of more than 20,000 people in the US, France, England and Japan and combining the results with molecular studies in the laboratory, the team discovered a common genetic signature. This may predict a higher risk of small vessel disease in the lungs, called pulmonary hypertension and its most serious form, pulmonary arterial hypertension. These results will influence the development of drug therapies that target the body’s response to oxygen limitation.

“This new level of knowledge will help identify people who may be at higher genetic risk for pulmonary hypertension and improve precision medicine techniques to provide personalized treatment,” said lead author Stephen Chan, a cardiologist at the University of Pennsylvania. Chairman of the Department of Vascular Medicine and Director of the Pittsburgh Institute of Vascular Medicine.

Using a combined approach of genomics and biochemistry, Chan’s lab discovered a pair of genes that play important roles in regulating metabolism and blood vessel disease. This pair of genes included a long non-coding RNA molecule (a messenger that promotes the transformation of the body’s genetic code into protein productss) and protein-binding partner, and their interaction was often active in cells exposed to low levels of oxygen compared to normal cells.

Taking the results even further, the team found that A change in a single DNA letter that controls the expression of this RNA-protein pair under low-oxygen conditions has been associated with an increased genetic risk of pulmonary hypertension. in different patient populations.

Pulmonary hypertension is almost an orphan disease, and the limited number of patients with pulmonary hypertension makes it difficult to find genetic variations that are rare but still important, Chan said. sufficient impact to overshadow individual differences.

With this in mind, scientists turned to collaborators around the world and to publicly available research datasets such as ‘All of us’ (a national health registry funded by the National Institutes of Health) to ensure that the results are relevant to the world’s diverse population.

Chan hopes his discoveries will stimulate developmenttargeted therapy related to oxygen sensitivity in the lining of blood vessels and that their pending patent application will advance the development of an entirely new field of epigenetic and RNA drug therapies that work not by manipulating the genome, but by changing the way it is read.