A Surprising Genetic Risk Factor For Type 2 Diabetes Is Discovered

12/26/2013 02:56pm ET | Updated January 25, 2014
FILE - The March 20, 2009 file photo shows the prehistoric Neanderthal man "N", left, as he is visited for the first time by another reconstruction of a homo neanderthalensis called "Wilma", right, at the Neanderthal museum in Mettmann, Germany. The world famous fossil "N" is estimated being about 40.000 years old; "Wilma" was built by Dutch artists Alfons and Adrie Kennis for the National Geographic magazine on a skeleton from the American museum of natural history in New York. Theories about when the last Neanderthals walked the Earth may have to be revised, according to a study that suggests they became extinct in their last refuge in Spain much earlier than previously thought. Previous dating of bone fossils found at Neanderthal sites in the region put the youngest at about 35,000 years. But researchers from Australia and Europe re-examined the bones using an improved method to filter out contamination and concluded that the remains are about 50,000 years old. (AP Photo/Martin Meissner, file)

All environmental factors being equal, Mexican Americans and other Latinos are at nearly twice the risk of developing Type 2 diabetes than any other ethnic group. Now, an international research group known as the SIGMA (Slim Initiative in Genomic Medicine for the Americas) Type 2 Diabetes Consortium, may be a step closer to understanding why.

In the largest ever genetic study of its kind, researchers publishing in the journal Nature conducted a DNA analysis of more than 8,000 residents of Mexico and people who lived in Latin America and discovered a gene variant that highly correlates to developing the disease.

People who carry one copy of the variant of this gene, named SLC16A11, have a 25 percent greater risk of developing Type 2 diabetes, while those who inherit the gene variant from both parents -- meaning they have two copies of it -- have a correlating 50 percent risk of developing the disease.

The researchers estimate that this SLC16A11 variation accounts for about 20 percent of Latinos' increased risk of Type 2 diabetes.

Approximately half of people with recent indigenous American ancestry -- which includes those of Mexican descent -- have this genetic variation. It is exceedingly rare among those of European extraction, about 2 percent of whom carry it, though 20 percent of those with East Asian ancestry also have the marker. Of particular intrigue for the researchers was the fact that the variant is absent in African populations. That's unusual because all humans originally came from Africa, which implies that this particular gene developed after humans left the continent.

In order to understand this unusual pattern, the team conducted additional genomic analyses, in collaboration with Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology, and discovered that the SLC16A11 sequence associated with risk of type 2 diabetes is found in a newly sequenced Neanderthal genome. Analyses indicate that the higher risk version of SLC16A11 was introduced into modern humans through mixing with Neanderthal.

Inheriting a gene from Neanderthal ancestors is actually not uncommon: approximately 1 to 2 percent of the sequences present in all modern day humans outside of Africa were inherited from Neanderthals. Importantly, neither people with diabetes nor populations of Native American or Latin American ancestry have an excess of Neanderthal DNA relative to other populations.

After leaving Africa, humans interbred with a population of Neanderthals some 60,000-70,000 years ago, reported the BBC.

"As far as I know, this is the first time a version of a gene from Neanderthal has been connected to a modern-day disease," Harvard geneticist, David Altshuler told NPR's Shots blog, although he noted that there is no evidence this distinct species of human had the disease, merely that they carried a marker for it.

The gene is expressed in the liver and is involved in the transportation of metabolites that affect fat levels in cells. By altering the level of the gene variant's proteins, researchers found that they were able to affect the amount of a type of fat that is linked to Type 2 diabetes.

"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," co-author José Florez, 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, said in a statement.

"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,” added 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.