Typically diagnosed in people older than 40, type 2 diabetes is caused by the combined action of genetic susceptibility and environmental factors. Diabetes is also known to be polygenic, meaning more than one gene contributes to the condition. In fact, various studies have identified more than 70 distinct genome locations carrying common variants. Now, scientists who performed a genetic analysis of about 3,700 DNA samples have identified a gene variant linked to higher prevalence — five times as high — of type 2 diabetes among Mexican and U.S. Latinos. The researchers hope these fresh findings, published Tuesday in JAMA, will improve screening as well as treatments for this vulnerable population.

Type 2 Diabetes

Insulin is necessary for the body to be able to use glucose, which is broken down from food, for energy. In type 2 diabetes, your body either does not produce enough insulin or your cells resist the insulin. When glucose builds up in the blood instead of going into cells, it can immediately cause your cells to be starved for energy. Over time, high blood glucose levels may hurt your eyes, kidneys, nerves, and heart.
Latino populations, which include all people who can trace their origins to Spanish cultures, have one of the highest rates of type 2 diabetes worldwide. In fact, experts estimate the percentage of people with type 2 diabetes, one of the leading causes of death among Mexican adults, was about 14 percent in Mexico’s 31 states during 2006. In the U.S., based on statistics from 1999 through 2002, the prevalence of (diagnosed) diabetes was 10 percent among Mexican-Americans, compared to just 5.2 percent among European-Americans. Although environmental factors, such as diet, in all likelihood explain most of this health disparity, genetic variants in the gene SLC16A11 may also be linked to this higher rate of type 2 diabetes among Latinos.

To further explore the genetic basis of diabetes, Dr. Karol Estrada, of the Broad Institute of Harvard and MIT, and colleagues with the SIGMA Type 2 Diabetes Consortium, performed whole-exome (part of the genome) sequencing on DNA samples from 3,756 Mexican and U.S. Latino individuals (1,794 with type 2 diabetes and 1,962 without diabetes) recruited from 1993 to 2013. This type of sequencing and analysis was chosen, in part, because it can capture not only common but also rare genetic variants in the protein-coding regions of genes. In other words, more subtle variations can be identified using this method.

What did the team of researchers discover? A single rare variant of the HNF1A gene (the p.E508K variant) was associated with about a five times higher odds of type 2 diabetes, though not early-onset diabetes. This variant was observed in 0.36 percent of participants without type 2 diabetes and 2.1 percent of participants with diabetes. The effects of this variant — a frequency of more than one in 1,000 — is the largest observed to date for any diabetes variant.

"Approximately 4 in a thousand people in Latino populations carry p.E5O8K, and these individuals have a 5-fold increase in prevalence for type 2 diabetes...," the authors noted. They further explained that identifying such genetic factors linked to type 2 diabetes might improve risk prediction, screening, and even treatment options.

Source: Estrada K, Aukrust I, Bjorkhaug L, et al. Association of a Low-Frequency Variant in HNF1A With Type 2 Diabetes in a Latino Population. JAMA. 2014.