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When genetic and environmental factors combine to cause high levels of fats, known as triglycerides, in the bloodstream, this is called hypertriglyceridemia. the condition impacts over 25% of all American adults, but most attempts to determine its genetic contributors have focused on patients of European ancestry, leaving research gaps for patients of other ethnicities.

High triglyceride levels increase the risk of cardiovascular and other diseases, including pancreatitis. Addressing underrepresentation among other racial and ethnic groups is essential to addressing inequities and improving diagnostics and health care.

An arteriole with restricted blood flow is one possible result of high triglyceride levels.

A team of researchers in the medicine department at the sought to address this knowledge gap by determining genetic risk factors for high triglyceride levels in American patients of African ancestry. Using the National Institutes of Health’s database, they identified a cohort of patients based on ancestry, age and medical history, and grouped them based on hypertriglyceridemia severity.

The researchers searched for variants in genes involved in triglyceride metabolism and compared their occurrence in each of the groups. They used bioinformatics tools to predict which of these variants are likely to be functional, changing the protein product of the gene.

The team’s analyses confirmed that Americans of African ancestry with high triglyceride levels are more likely to carry certain genetic risk factors compared to those with normal levels. These factors include functional variants in regions encoding lipoprotein lipase, an essential enzyme in triglyceride breakdown, and apolipoprotein A5, a primary regulator of triglycerides in the blood, as well as other genetic factors.

According to QiPing Feng, an associate professor of medicine at Vanderbilt and corresponding author of the study, , published recently in the Journal of Lipid Research, reinforce a genetic basis for hypertriglyceridemia.

“This will enable us both to identify patients at risk and to treat patients with high triglyceride levels to prevent cardiovascular disease,” Feng said.

The results are a crucial advance in hypertriglyceridemia research, but genetics do not seem to give the full picture.

“Even though we have screened several different categories of potential genetic factors, we still have around half of patients with high triglycerides for which we cannot identify any genetic factor,” Feng said.

This may be due to environmental factors such as stress.

The All Of Us depository includes genetic data, medical records and extensive questionnaires completed by patients. Feng’s team plans to use this data to research the contribution of environmental factors moving forward.

“We really appreciate both the program,” Feng said, “and the participants in All Of Us that agreed to donate their data for this kind of analysis.”