A new genetic risk factor for type 2 diabetes has been been identified in the Mexican and Mexican American population which increases the risk of obtaining diabetes by 25% for a person who carries one copy of the gene. The diabetes risk gene, termed SLC16A11, has also been found in up to half of people who have recent Native American ancestry, including Latin Americans. The gene variant is found in about 20 percent of East Asians and is rare in populations from Europe and Africa.
For people who have inherited genes from both parents the risk factor is increased by 50%. Genes operate on a dominant and recessive trait principle, with inheritance of the genes from both sets of parents used as the precursor for expressing any trait, in this case the risk of obtaining diabetes. SLC16A11 is expressed in the liver and is characterized as part of a set of genes that code for proteins that transport metabolites. Altering the levels of the SLC16A11 protein can change the amount of a type of fat that has previously been implicated in the risk of diabetes. As a result of these findings the research team was led to hypothesize that SLC16A11 may be involved in the transport of an unknown metabolite that affects fat levels in cells and thereby increases risk of type 2 diabetes.
“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, a Broad associate member, an associate professor of medicine at Harvard Medical School and an Assistant Physician in the Diabetes Unit and the Center for Human Genetic Research at the Massachusetts General Hospital.
“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.”
“We conducted the largest and most comprehensive genomic study of type 2 diabetes in Mexican populations to date. 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. 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,” said Teresa Tusie-Luna, project leader at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán and principal investigator at the Biomedical Research Institute, National University of Mexico.
“One of the most exciting aspects of this work is that we’ve uncovered a new clue about the biology of diabetes,” said co-senior author David Altshuler, deputy director and chief academic officer at the Broad Institute and a Harvard Medical School professor at Massachusetts General Hospital (MGH). “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.”
Amy L. Williams, Teresa Tusié-Luna et al. Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico. Nature, 2013; DOI: 10.1038/nature12828