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New Diabetes-Related Genetic Risk Factor Discovered

December 26, 2013
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redOrbit Staff & Wire Reports – Your Universe Online

A previously undetected genetic risk factor could help explain why there is an elevated risk of type 2 diabetes among Mexican and other Latin American populations, according to a new study published online Wednesday in the journal Nature.

In the study, an international team of researchers known as the SIGMA (Slim Initiative in Genomic Medicine for the Americas) Type 2 Diabetes Consortium performed the largest genetic study to date in people of Mexican and Mexican-American descent. They discovered that people who had the higher-risk version of the gene SLC16A11 could be 25 percent more likely to have diabetes than those lacking said gene.

Furthermore, individuals who inherit copies from both patents are 50 percent more likely to have diabetes. The higher-risk version has been found in up to half of people with recent Native American ancestry (including Latin Americans) as well as 20 percent of East Asians, and elevated frequency of SLC16A11 in Latin American could account for up to one-fifth of the populations’ increased prevalence of diabetes, the authors explained.

“To date, genetic studies have largely used samples from people of European or Asian ancestry, which makes it possible to miss culprit genes that are altered at different frequencies in other populations,” said co-corresponding author José Florez, an assistant physician in the Massachusetts General Hospital Diabetes Unit. “By expanding our search to include samples from Mexico and Latin America, we’ve found one of the strongest genetic risk factors discovered to date, which could illuminate new pathways to target with drugs and a deeper understanding of the disease.”

“In addition to validating the relevance to Mexico of already known genetic risk factors, we discovered a major new risk factor that is much more common in Latin American populations than in other populations around the world,” added Teresa Tusie-Luna, principal investigator at the National University of Mexico’s Biomedical Research Institute. “We are already using this information to design new studies that aim to understand how this variant influences metabolism and disease, with the hope of eventually developing improved risk assessment and possibly therapy.”

According to BBC News Science Editor Paul Rincon, the SLC16A11 sequence discovered by the SIGMA team was found in a recently sequenced Neanderthal genome originating from Denisova cave in Siberia. That would suggest, he explained, that the gene variant might have been inherited by the ancient, now-extinct species of early human.

This marks the first time that SLC16A11, which belongs to a family of genes that code for proteins that transport metabolites, has been identified as factoring into a human disease. As such, the researchers said that little information was previously available about its function. The study authors report that SLC16A11 is expressed in the endoplasmic reticulum, a cellular structure located within the liver.

Furthermore, the SIGMA investigators went on to demonstrate that altering levels of the protein could change the amount of a type of fat that had previously been implicated in the risk of diabetes. That discovery led the team to hypothesize that SLC16A11 could be involved in the transport of an unknown metabolite – a metabolite which affects fat levels in cells, resulting in an increased risk of type 2 diabetes.

“One of the most exciting aspects of this work is that we’ve uncovered a new clue about the biology of diabetes. We are now hard at work trying to figure out what is being transported, how this influences triglyceride metabolism, and what steps lead to the development of type 2 diabetes,” said co-senior author David Altshuler of the Broad Institute. He and his colleagues ultimately hope use to these insights about SLC16A11 to discover new drug targets for treating the disease.


Source: redOrbit Staff & Wire Reports - Your Universe Online