A genetic variant near the KLF14 gene regulates hundreds of genes that govern how and where women’s bodies store fat, which affects their risk of developing Type 2 diabetes, according to research presented on Saturday, October 10, at the American Society of Human Genetics (ASHG) 2015 Annual Meeting in Baltimore, Maryland. Specifically, different alleles, or versions, of the variant cause fat-storing cells to function differently. “At the whole-body level, these differences between alleles are not associated with changes to overall weight or body mass index, but they do affect women’s hip circumference,” explained Kerrin Small, Ph.D., Head of the Genomics of Regulatory Variation Research Group at King’s College London and lead author on the study. “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,” she said. The variant is located near the KLF14 gene, which encodes a protein that Dr. Small and her colleagues discovered directly regulates the expression of hundreds of other genes in fat tissue. KLF14 is maternally imprinted, which means that a person’s expression of KLF14 and the resulting effects on fat tissue are determined by the version of the gene inherited from his or her mother; the father’s allele does not affect levels of this regulatory protein. Researchers first identified the relationship between the variant near KLF14 and Type 2 diabetes risk in a large, genome-wide association study of a broad population.
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