Researchers investigating heart disease factors in an Amish community found some of them had a gene variant that seemed to keep down levels of triglycerides or blood fats, and may also be involved in keeping arteries clear of blockages since only those who had it were relatively free of arterial calcification.

The study was the work of geneticist Dr Toni Pollin and endocrinologist Dr Alan Shuldiner from the University of Maryland School of Medicine in Baltimore, and colleagues, and is published online in the 12 December issue of Science.

Studies have shown that different people have different responses to fatty foods. Unused calories become triglycerides which increase the risk of heart disease and stroke, and some people have much higher levels of these blood fats. While diet is an obvious factor, some genes are also thought to play a role, for example when mice don’t have the AP0C3 (short for Apolipoprotein C-III) gene they have low levels of triglycerides, regardless of what they eat. And coronary artery disease is thought to be related to this gene because it inhibits hydrolysis of triglycerides (ie their elimination).

Pollin, Shuldiner and colleagues invited 800 healthy adult male and female members of the Old Order Amish in Lancaster County, Pennsylvania to take part in a genome-wide association study where they had short term exposures to a range of environmental factors, such as eating a high salt diet, and then underwent a range of clinical exams.

This Amish community is quite cut off from the outside world and members tend to marry each other, creating an interesting population for geneticists because of the relatively higher proportions of people with the same gene variants compared to the world at large, making it easier to search for particular disease genes.

The researchers found that about 5 per cent of the Lancaster Amish had one of their inherited AP0C3 genes switched off (they were heterozygous carriers of a null mutation called R19X), which meant they had only half the AP0C3 expression of most other people.

For this particular study the researchers then observed the effect of drinking a 782-calorie milkshake, “primarily heavy whipping cream,” Pollin commented to ScienceNOW.

They found that compared to non-carriers, the carriers of the switched off AP0C3 variant:

  • Had lower levels of triglycerides (fasting and post-prandial), higher levels of HDL cholesterol (the so-called “good” cholesterol) and lower levels of LDL cholesterol (the so-called “bad” cholesterol), and
  • Were less likely to have coronary artery calcification, an early sign of blocked arteries or atherosclerosis.

The researchers said these results suggested that “lifelong deficiency” of AP0C3 had a “cardioprotective effect”.

Dr Anne Tybjærg-Hansen, a researcher who investigates genetics and heart disease at Copenhagen University Hospital in Denmark, told ScienceNOW that this study shows there is a link between this variant of AP0C3 and how the body deals with triglycerides. However, the Amish population is unique, so “the mutation they found is probably not a mutation that you’re going to find in other populations,” she said.

In fact Pollin herself comments in the paper that they did not find the variant at all in a sample of 200 healthy Caucasians.

Tybjærg-Hansen said the study showed a clear link between AP0C3 and triglycerides, and there may well be other mutations of the gene.

“A Null Mutation in Human APOC3 Confers a Favorable Plasma Lipid Profile and Apparent Cardioprotection.”
Toni I. Pollin, Coleen M. Damcott, Haiqing Shen, Sandra H. Ott, John Shelton, Richard B. Horenstein, Wendy Post, John C. McLenithan, Lawrence F. Bielak, Patricia A. Peyser, Braxton D. Mitchell, Michael Miller, Jeffrey R. O’Connell, and Alan R. Shuldiner.
Science Vol. 322. no. 5908, pp. 1702 – 1705, 12 December 2008.
DOI: 10.1126/science.1161524

Click here for Abstract.

Sources: Science and ScienceNOW.

Written by: Catharine Paddock, PhD