Ancient Arctic Gene Variants May Increase The Risk of Modern Diseases Among Greenlanders

Over the past 25 years, Greenland’s population has experienced a marked increase in so-called cardiometabolic diseases, including type 2 diabetes and cardiovascular disease.

Previous studies have already identified links between the rise in these diseases and genetic variants that are common among Greenland's Inuit population.

However, how these gene variants actualle raise disease risk has remained largely unclear.

More than 3,700 blood samples

To understand the underlying biological mechanisms, researchers at the University of Copenhagen analysed blood samples from more than 3,700 Greenlanders, collected through extensive public health surveys over a 20-year period.

Using advanced measurement methods, they mapped levels of 177 blood proteins associated with inflammation and heart health.

The work identified 251 genetic variants that influence protein levels in the blood of Greenlanders, 70 of which were previously unknown.

"By understanding how genetic variants regulate proteins in the blood, we can identify new drug targets and understand why certain populations are more susceptible to specific diseases," Professor Torben Hansen at the Novo Nordisk Foundation Center for Basic Metabolic Research told MedicalXpress last year.

Newly discovered genetic variant

The study shows that genetic control of specific proteins is significantly stronger among Greenlandic Inuit than among European populations.

A variant of the CPT1A gene, which likely helped Inuit digest traditional, high-fat Arctic diets from marine mammals, now appears to have a dampening effect on the body’s inflammatory responses.

At the same time, a variant in the TBC1D4 gene affects immune-system protein levels and is now thought to contribute to up to 10 percent of all diabetes cases in Greenland.

Researchers also discovered an entirely new genetic variant that regulates inflammatory proteins in the blood and was associated with a 31 percent increased risk of cardiovascular disease among Greenlanders.

Distinct genetic history

Greenlandic Inuit have lived relatively isolated for many generations under extremely demanding Arctic conditions.

At the same time, they have relied on a diet in which fish and marine mammals such as seals and whales have been key sources of fat and protein.

Over long periods, such living conditions may have led to certain genetic variants becoming more common in the population. Several of these variants now influence how the body regulates fat, energy, inflammation and blood sugar.

According to the researchers, the findings provide new insight into how genetic adaptations to an Arctic environment can affect disease risk in present-day Greenland.