Approved Research

Study on novel genetic mutations associated with newly-defined refractory hypertension phenotypes.

Lay summary

Blood pressure is a product of the combined action of cardiac output and peripheral vascular resistance, and is regulated by many factors. Blood pressure is a multifactorial trait, and multiple complex molecular mechanisms affect the final blood pressure phenotype. Essential hypertension is one of the most common cardiovascular diseases and an important risk factor for common diseases that lead to human death (such as stroke, coronary artery disease, heart failure, etc.). Refractory hypertension is defined as a blood pressure level that is above the target value despite the use of at least three antihypertensive drugs (including diuretics) at optimal doses. Studies have shown that 20% of patients with hypertension have refractory hypertension, and patients with extremely refractory hypertension account for 5% of patients with refractory hypertension. The diagnosis and treatment process of refractory hypertension is complicated, and the treatment methods are few. Till now, SNPs found in GWAS studies can only explain about 27% of the inherited hypertension phenotype, and further genetic studies are needed. Therefore, it is urgent to study the pathogenesis of refractory hypertension to provide new diagnosis and treatment methods.

In recent years, the scientific community has continued to pay attention to the genetic factors that lead to essential hypertension. However, since the pathogenic causes of essential hypertension are different, normal genetic analysis using blood pressure as the only phenotype may overlook certain pathogenic mutations that lead to certain types of hypertension. This study aims to identify novel hypertension-associated genetic mutations that could cause a specific type of hypertension. In this 36-month study, we plan to characterize refractory hypertension patients from UK Biobank with newly defined phenotypes and study the association of novel pathogenic genes with defined phenotypes. The discovery of new pathogenic mutations for hypertension is conducive to the establishment of new diagnostic methods for refractory hypertension and the development of new anti-hypertension drugs targeting the relevant mutations and pathways.