New research into the genetics of diabetes revealed a previously unknown risk factor associated with type 2 diabetes in the Mexican and Latin American populations, according to a letter published in Nature.
In an effort to determine an origin for the increased risk of diabetes among these populations, the researchers of the Slim Initiative in Genomic Medicine for the Americas (SIGMA) analyzed 9.2 million single nucleotide polymorphisms in 3,848 patients with type 2 diabetes and 4,366 controls from Mexico and Latin America. They identified a novel locus across the solute carriers SLC16A11 and SLC16A13, with four amino acid substitutions on SLC16A11 present in nearly 50% of the population from the Americas.
“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,” María T. Tusié-Luna, MD, PhD, 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, said in a press release.
SIGMA researchers found that patients carrying the risk haplotype developed type 2 diabetes on average 2.1 years earlier and at a lower BMI than those without the haplotype. Each copy of the haplotype confers a 20% increased risk for diabetes; if an individual carries two copies of the haplotype, one from each parent, the risk for developing diabetes could be as high as 50%, according to the press release.
This haplotype is rare or absent in European and African samples and occurs in about 10% of East Asian samples. The researchers attributed the frequency in the Americas to an early mixture of humans with Neanderthals.
“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,” José C. Florez, MD, PhD, associate professor of medicine at Harvard Medical School and assistant physician in the diabetes unit and the Center for Human Genetic Research at Massachusetts General Hospital, said in a press release. “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.”
According to the data published, the SLC16A11 messenger RNA is expressed in the liver, salivary gland and thyroid. The SLC16A11 protein localizes to the endoplasmic reticulum where, once expressed in heterologous cells, alters the lipid metabolism and causes an increase in intracellular triacylglycerol levels and intracellular diacylglycerols along with decreases in lysophosphatidylcholine, cholesterol ester and sphingomyelin lipids, researchers wrote. This indicates SLC16A11 may have a role in hepatic lipid metabolism, they wrote.
“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,” Tusié-Luna said.
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