Mutation in Fat-storage Gene Linked to Type 2 Diabetes

After studying an Amish population, researchers at the University of Maryland Medical Center have discovered a mutation in a fat-storage gene that increases a patient’s risk for type 2 diabetes.

For their study published May 21, 2014, in the New England Journal of Medicine, the researchers examined a mutation in the LIPE gene that is responsible for encoding the hormone-sensitive lipase (HSL) enzyme “involved in breaking down stored fat (triglycerides) into fatty acids.”

Of the 2,738 Amish study participants, the investigators focused on 12 lipolytic-pathway genes in 24 participants who had high fasting serum triglyceride levels. In one patient with extremely high triglyceride levels, the investigators discovered “a 19-bp deletion in exon 9 of LIPE.”

From there, the researchers found 140 of the participants were heterozygous for the deletion trait (ID genotype), while one was homozygous for it (DD genotype). According to the authors, Amish populations disproportionately carry the D allele compared to other non-Amish people of European descent (5.1% versus 0.2%).

“Western blot analysis of white-adipose-tissue extracts showed no detectable HSL protein in participants with the DD genotype and approximately a 50% reduction in HSL protein in participants with the ID genotype,” the researchers wrote.

In comparison to non-carriers (II genotype), participants with the ID genotype were found to be 1.8 times more likely to be diagnosed with type 2 diabetes. Despite having body mass indexes (BMIs) similar to non-carriers, “all 4 participants with the DD genotype received a diagnosis of (type 2 diabetes) before 50 years of age,” the researchers claimed.

Moreover, in a subgroup of 52 women with similar ages and BMIs, 3 participants with the DD genotype had less fat in their lower extremities than those with the II and ID genotypes .

"Future studies of this gene will allow us to look more closely at the effects of its deficiency on human metabolism to better understand the function of the HSL protein and its impact on fat and glucose metabolism," senior study author Coleen M. Damcott, PhD, said in a statement. "These studies will also examine the potential of using HSL as a drug target for treating (type 2 diabetes) and related complications."