Master regulator gene linked to metabolic traits

Small KS. Nat Genet. 2011;doi:10.1038/ng.833.

A team of researchers from King’s College London and the University of Oxford have identified a “master regulator” gene linked to type 2 diabetes and cholesterol levels that controls the behavior of other genes found within fat in the body, according to a press release.

The researchers said that the regulatory gene — identified as KLF14 — could be a potential target for future treatments against obesity, cardiovascular disease and diabetes.

“KLF14 seems to act as a master switch, controlling processes that connect changes in the behavior of subcutaneous fat to disturbances in muscle and liver that contribute to diabetes and other conditions. We are working hard right now to understand these processes and how we can use this information to improve treatment of these conditions,” Mark McCarthy, MD, PhD, University of Oxford, said in the release.

The MuTHER study, published in Nature Genetics, was part of a large, multinational collaboration funded by the Wellcome Trust. It involves researchers from King’s College London, University of Oxford, The Wellcome Trust Sanger Institute and the University of Geneva; deCODE Genetics also contributed to results reported in the study.

The link between the KLF14 gene and type 2 diabetes and cholesterol levels is known. However, until now, the nature of the association and the role KLF14 played in controlling other genes located on the genome remained unknown.

The researchers examined more than 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. The association was confirmed in an independent sample of 600 subcutaneous fat biopsies from Icelandic participants.

The activity of KLF14 is inherited from the mother, and the gene has the ability to control other genes linked to a range of metabolic traits, including BMI, cholesterol, insulin and glucose levels.

“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. This has great therapeutic potential particularly, as by studying large detailed populations, such as the twins, we hope to find more of these regulators,” Tim Spector, MD, MSc, FRCP, department of twin research at King’s College London, said in the release.

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