Two variants associated with the risk of pulmonary arterial hypertension
Variants near SOX17 gene and HLA-DPA1/DPB1 have been found to have been found in genomes of individuals with pulmonary arterial hypertension.
2085 patients involved in four different studies had mutations at odds ratio 1:56 – 1:80.
Rare changes in SOX17 gene was previously associated with pulmonary arterial hypertension, but the new research points to an enhancer before the gene – a sequence influencing the regulation of SOX17. The modification results in the change of activity in endothelial cells in blood vessels. Experimental reflection of enhancer mutations showed that SOX17 is deactivated and therefore contributes to the risk of the disease.
Variants of HLA-DPA1/DPB1 were found to influence not only the risk but also an age of diagnosis and mortality of an individual.
More: “Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis”, C. Rhodes et al., 2018, doi:10.1016/S2213-2600(18)30409-0.