A team of researchers, led by King’s College London and the University of Oxford, have found that a gene linked to type 2 diabetes and cholesterol levels is in fact a “master regulator” gene, which controls the behavior of other genes found within fat in the body.
As fat plays a key role in susceptibility to metabolic diseases such as obesity, heart disease and diabetes, this study highlights the regulatory gene as a possible target for future treatments to fight these diseases.
It was already known that the KLF14 gene is linked to type 2 diabetes and cholesterol levels but, until now, how it did this and the role it played in controlling other genes located further away on the genome was unknown.
The researchers examined over 20,000 genes in subcutaneous fat biopsies from 800 UK female twin volunteers. They found an association between the KLF14 gene and the expression levels of multiple distant genes found in fat tissue, which means it acts as a master switch to control these genes. This was then confirmed in a further independent sample of 600 subcutaneous fat biopsies from Icelandic subjects.
These other genes found to be controlled by KLF14 are in fact linked to a range of metabolic traits, including body-mass index (obesity), cholesterol, insulin and glucose levels, highlighting the interconnectedness of metabolic traits.
The KLF14 gene is special in that its activity is inherited from the mother. Each person inherits a set of all genes from both parents. But in this case, the copy of KLF14 from the father is switched off, meaning that the copy from the mother is the active gene — a process called imprinting.
“This is the first major study that shows how small changes in one master regulator gene can cause a cascade of other metabolic effects in other genes,” Tim Spector, professor in the department of twin research at King’s College and MuTHER project leader, stated in a press release. “This has great therapeutic potential particularly as by studying large detailed populations such as the twins we hope to find more of these regulators.”