Researchers discover underlying genetics, marker for stroke and cardiovascular disease

March 25, 2014

Scientists studying the genomes of nearly 5,000 people have pinpointed a genetic variant tied to an increased risk for stroke, and have uncovered new details about an important metabolic pathway that plays a major role in several common diseases. Their findings may provide new clues to underlying genetic and biochemical influences in the development of stroke and cardiovascular disease, and may also help lead to new treatment strategies. Stephen R. Williams, PhD, and his team reported the findings in PLoS Genetics.

The researchers focused on a biochemical pathway called the folate one-carbon metabolism (FOCM) pathway. They knew that abnormally high blood levels of the amino acid homocysteine are associated with an increased risk of stroke and cardiovascular disease. Homocysteine is a breakdown product of methionine. But clinical trials of homocysteine-lowering therapies have not prevented disease, and the genetics underlying high homocysteine levels—and methionine metabolism gone awry—are not well defined.

The researchers conducted genome-wide association studies of participants from two large long-term projects: the Vitamin Intervention for Stroke Prevention (VISP), a trial looking at ways to prevent a second ischemic stroke, and the Framingham Heart Study (FHS), which has followed cardiovascular health and disease in a general population for decades. They also measured methionine metabolism—the ability to convert methionine to homocysteine—in both groups.

Investigators identified variants in five genes in the FOCM pathway that were associated with differences in a person’s ability to convert methionine to homocysteine. They found that the ALDH1L1 gene was also strongly associated with stroke in the Framingham study. They also made important discoveries about the methionine-homocysteine process. They plan to study the other four genes in the pathway to try to better understand their potential roles in stroke and cardiovascular disease risk. Read the study.

Read more