In the latest issue of Nature Genetics, an international research team featuring Prof.
Hypertension, also called the ‘silent killer’, is one of the most prevalent illnesses in humans and is the main cause of strokes and infarctions. It has a significant genetic component, but the precise mechanisms responsible for predisposition to hypertension are still largely unknown.
The research team’s interest in kidneys was sparked by the fact that they are a key organ when it comes to blood pressure regulation, hypertension and antihypertensive treatment. What is more, 80% of the identified genes have not been previously considered related to hypertension. The team, led by Prof. Maciej Tomaszewski from the University of Manchester, focused on how the information inherited through DNA translates into genetic predisposition towards hypertension via the activity of some kidney genes. Their study entailed complex analyses of kidney tissue on various molecular ‘levels’, combining DNA, RNA and DNA methylation (responsible for gene expression) from the same set of samples. To define the causal relationship between thousands of studied genes and hypertension, the scientists have used a statistical method known as Mendelian randomisation.
Some of the identified genes are those that impact the structure and functioning of kidneys (WDR73), while others have been previously linked to diabetes (KCNJ11) or, interestingly, the immune system (IRF5 and IRAK1BP1).
The paper is particularly important, since some of these genes can be targeted by already known drugs, enabling new ways of combating hypertension. A number of the identified genes are also therapeutic goals of antihypertensive medicine. For instance, KCNJ11 was identified as a goal for minoxidil and diazoxide, while GUCY1A3 was identified as a goal for nitrates and riociguat. It is highly probable that similar analyses of the newly identified mechanistic genes could point to potential new antihypertensive therapies.