What can a small village nestled in the mountains of Crete teach us about cardiovascular disease control? A whole lot, according to a new study from the Wellcome Trust Sanger Institute in Cambridge, UK.  Researchers have shown that inhabitants of the tiny Greek community have evolved a rare gene variant that appears to protect them from health risks associated with a high-fat diet and weight gain. The discovery could have significance for the development of new therapies and prevention strategies against heart disease, stroke, and metabolic disorders.

All the Cheese, None of the Consequences

Prevailing research suggests that a high-fat diet rich in cheese, lamb, and pastries is an unsustainable habit that eventually sends the body into a downward spiral marked by chronic disease and adverse biological events. However, it would appear that this information has yet to reach the Cretan village of Anogia and its surrounding Mylopotamos municipalities, where some residents seem to eat whatever they want without experiencing any consequences. "The Mylopotamos villages residents have the same rate of diabetes as the general Greek population but do not suffer from disease complications," Eleftheria Zeggini, a professor and lead author of the current study, said in a press release

The study, which is published in the journal Nature Communications, sought to get to the bottom of this epidemiological hiccup. Specifically, the authors wanted to know whether the population expressed R19X — a rare, protective gene variant of APOC3 first recorded in the Amish population in 2008. According to Zeggeni, this variant is associated with decreased levels of triglyceride, a blood fat that has been shown to increase the risk of heart disease. It also promotes higher levels of high density lipoproteins, or “good” cholesterol.

To investigate, the research team collected genetic samples from 1,200 from people living in Anogia and the surrounding Mylopotamos. They found that the protective gene variant occurred in 2 percent of the villagers — 40 times the estimated European prevalence of 0.05 percent. “This work exemplifies the value of isolated populations in successfully detecting transferable rare variant associations of high medical relevance,” the authors wrote.

Medical Breakthroughs through Anthropological Discovery

The Anogian community is by no means the only population isolate relevant to current research. Another example can be found in the remote villages of Ecuador, where residents are known for their short stature and seemingly innate immunity to cancer and diabetes. It is widely believed that the secret to a significantly longer lifespan is locked away in the genomes of these villagers.  

“I discovered the population in 1987,” Jaime Guevara-Aguirre, an Ecuadorean physician and diabetes expert, told The New York Times. “In 1994, I noticed these patients were not having cancer, compared with their relatives.”

Some experts argue that these Ecuadorians owe their virtually non-existent cancer rates to the genetic disorder that prevents their bodies from reaching a normal height. This rare type of dwarfism, called Laron syndrome, is thought to reduce the body’s levels of the hormone IGF-1. For reasons that are not entirely clear, this reduction appears to rein in DNA damage and spur the destruction of damaged cells.

Hopefully, the continued pursuit of these unique population isolates will help scientists identify new, effective genetic target for drug research. "Our work exemplifies the importance of studying these isolated populations,” Ioanna Tachmazidou, first author of the Anogia cohort study, told reporters. "APOC3 is a gene that is relevant to all populations. This type of study can increase the pace of new therapeutic treatments against cardiovascular and metabolic disease."

Source: Tachmazidou I, Dedoussis G, Southam L et al. “A rare functional cardioprotective APOC3 variant has risen in frequency in distinct population isolates.” Nature Communications 4. 2013.