A genetic variant governs how and where fat is stored in women, which affects their risk of type 2 diabetes, according to new research.
The findings were presented at the American Society of Human Genetics (ASHG) 2015 Annual Meeting in Baltimore by Dr. Kerrin Small, PhD and Head of the Genomics of Regulatory Variation Research Group at King’s College London.
This variant is located near the KLF14 gene, which directly regulates where fat is stored in women. Different alleles (versions) of this variant lead to fat-storing cells functioning differently.
As KLF14 is maternally imprinted, a person’s expression of KLF14 and function of fat tissue is determined by which version of the gene has been inherited by a person’s mother. Small’s team reported that the father’s allele does not affect levels of KLF14.
Effect on type 2 diabetes risk
The effect on type 2 diabetes was assessed after Small and her colleagues focused on female participants in a large study investigating this variant and type 2 diabetes.
Women who inherited this variant were significantly more likely to develop type 2 diabetes, but the researchers are still exploring why the variant only seems to affect women.
One theory is that men never attain the levels of the KLF14 mRNA transcript – a precursor to the KLF14 protein – which causes an increased type 2 diabetes risk, while a second hypothesis is that a sex-specific protein may interact with KLF14 and alter its effect in men or women.
Dr. Small said: “Previous studies have shown that on average, women who carry fat in their hips – those with a “pear-shaped” body type – are significantly less likely to develop diabetes than those with smaller hips. Looking at the variant we studied, large-scale genome-wide association studies show that women with one allele tend to have larger hips than women with the other one, which would have a protective effect against diabetes.
“These findings have important implications as we move toward more personalized approaches to disease detection and treatment. If we can identify the genes and protein products involved in diabetes risk, even for a subset of people, we may be able to develop effective treatment and prevention approaches tailored to people in that group.”
Dr. Small’s team are now investigating how the variant near KLF14 specifically affects KLF14 expressio, and how many genes regulated by KLF14 affect type 2 diabetes risk and fat storage patterns.

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