High triglyceride levels have long been associated with the development of heart disease but until researchers at the University of Maryland tapped into the nearby Amish gene pool, no identifiable link had been found. Now however, researchers say they’ve not only discovered the missing link, they’ve traced it back to a common ancestor from the 1700s.
Assistant professor Toni I. Pollin and her colleagues treated 809 members of Lancaster, Pennsylvania’s Old Order Amish community to milkshakes richly laced with heavy cream. They then monitored their study subjects’ bloodstreams for six hours to follow each individual’s ability to digest this high influx of fat.
In about 95% of the individual cases, levels of triglycerides responded as expected. The level of this common fat of the bloodstream rose steadily during the first three or four hours as the milkshakes were being digested and then it dropped back to pre-milkshake levels again.
The triglyceride response of the remaining 5% of the study subjects, however, proved quite surprising. In these people, triglyceride levels fluctuated very little during the entire six-hour study period.
As described in tomorrow’s issue of the journal, ‘Science,’ the lucky 5% shared a mutation of the gene apoC-III, which produces a protein called APOC3. As a rule, APOC3 slows the triglyceride processing mechanism but the mutation disables one of the two apoC-III genes, which, in turn, causes rapid triglyceride breakdown.
Steady triglyceride levels weren’t all the benefits the researchers found. These same study subjects had low levels of LDL cholesterol, high levels of which are known to increase one’s risk of developing heart disease. They also had high levels of HDL cholesterol, a factor linked to protection from heart disease. They even had less plaque in their arteries than most people of the same age and similar lifestyles.
The Amish settled in the United States about 14 generations ago and have remained close knit and isolated from mainstream society, a cultural characteristic that makes them ideal candidates for genetic study. The research team was able to trace the apoC-III mutation to a common ancestor born during the 18th century.
While the implications of Pollin’s findings are exciting, much research is still needed before any hope of developing a drug to manipulate APOC3 production is expected.