Silenced X gene not so quiet
Reue believes the gene responsible for this “evolutionary advantage” is on a female’s second X chromosome. Traditionally, researchers have considered this chromosome to be transcriptionally inactivated, meaning the body’s metabolism disregards it.
“It has long been thought that the genes on one of the two X chromosomes that a female inherits are not expressed, so both men and women have only one functional X chromosome. It turns out that this is not quite true,” she says. “A handful of genes are expressed on the inactivated X chromosome in females. Those genes are likely candidates for the effect of the second X chromosome on obesity.”
After testing those genes one by one in mice, Reue has settled on a promising candidate and is now conducting tests to validate that discovery.
The Statin Effect in women
As an offshoot of her work on diabetes, Reue is searching for the genes that dictate how the use of statins to control cholesterol levels induces diabetes in some people. The statin effect is far more prevalent in women than men.
“We’re only now recognizing this novel consequence of statin use,” she says. “By modeling statin adverse effects in the mouse, we hope to identify the corresponding genetic and sex components that dictate who may develop statin-related diabetes.”