Body shape, diabetes risk could be determined by a woman’s genes

These hips don’t lie! Different versions of a genetic variant could determine how and where a woman’s body stores fat, which in turn can help determine her body type and the likelihood she will develop diabetes, researchers from King’s College London have discovered.

Dr. Kerrin Small, head of the university’s Genomics of Regulatory Variation Research Group, and her colleagues reported at the American Society of Human Genetics (ASHG) 2015 Annual Meeting this weekend that the variant occurs near the KLF14 gene and helps regulate hundreds of other genes that determine how and where fat is stored in the female body.

Specifically, they explained, the different versions or “alleles” of this variant causes fat-storing cells to function differently, and these changes have a direct impact on a woman’s risk of Type 2 diabetes, the research team explained in a statement. While these differences do not directly alter weight or body mass index, they do affect hip circumference, Dr. Small explained.

“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,” she continued, adding, “Looking at the variant we studied… studies show that women with one allele tend to have larger hips than women with the other one.”

Why is this link only in women?

The gene which this variant is located near, the KLF14 gene, encodes a protein the study authors found to directly regulate the expression of hundreds of other genes in fat tissue. KLF14 is maternally imprinted, they added, meaning that a person’s expression of it (and the impact that it has on fat tissue) are inherited solely from the mother, not the father.

The link between the variant and Type 2 diabetes risk was originally identified through a large-scale, genome-wide association study, and the link was determined to be modest but statistically significant. However, when Dr. Small’s team focused specifically on women who inherited this allele from their mothers, the effect became more widespread. But why?

Dr. Small and her colleagues have discovered that females tend to have higher baseline levels of the KLF14 mRNA transcript, a precursor to the KLF14 protein, than males. What this indicates is that there may be a threshold effect in which men rarely if ever reach the levels required to up the risk of diabetes. Alternatively, a different, sex-specific protein could be interacting with the KLF14 protein, making it either stronger in men or weaker in women.

“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 said. “Eventually, we hope to develop a comprehensive, predictive model of how genes affect risk of Type 2 diabetes in women.”

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