3 replies to this topic

[manofsan]

A new study shows that a mutation of the APOC3 gene is tied to rapid breakdown of triglycerides:

http://www.nytimes.c...ch/12heart.html

[Mind]

I wonder since apoC-III is also regulated by insulin if a drug to target that gene will work as good as speculated.

Interesting study in that they could trace the mutation through the ancestry of the Amish community. I would like to see if the offspring of the one person who had the apoC-III mutation lived longer due to the fast metabolism of triglycerides, or had a lesser incidence of heart disease. That would really solidify the results of the study as something beneficial to pursue.

For the sake of heart disease research, 809 members of the Old Order Amish community agreed to go to a clinic in Lancaster, Pa., near their homes, and drink a rich milkshake that was made mostly of heavy cream. Over the next six hours, a group of investigators took samples of their blood, determining how much fat was churning through their bloodstreams.

Most of the study participants responded as expected — their levels of triglycerides, a common form of fat in the blood, rose steadily for three to four hours and then declined. But about 5 percent had an extraordinary reaction: their triglyceride levels started out low and hardly budged.

It turns out, the researchers report in the Friday issue of the journal Science, that those individuals who barely responded have a mutation that disables one of their two copies of a gene called apoC-III. The gene codes for a protein, APOC3, that normally slows the breakdown of triglycerides.

With the mutated gene, people break down triglycerides unusually quickly. And, the investigators find, they also have low levels of LDL cholesterol, which at high levels increases heart disease risk. They have high levels of HDL cholesterol, which is associated with a decreased risk of heart disease. And they appear to have arteries relatively clear of plaque.

To find the gene mutation, the researchers, led by Toni I. Pollin, an assistant professor of medicine at the University of Maryland School of Medicine, scanned the entire genomes of their study subjects, looking for genetic regions that were linked to levels of blood triglycerides. That led them to a region containing the apoC-III gene. When they sequenced it, they found the mutation that destroyed its function.

Dr. Alan R. Shuldiner, head of the division of endocrinology, diabetes and nutrition at the University of Maryland School of Medicine in Baltimore and the senior author of the paper, said that the Amish were ideal for the study because they were an isolated population that had been in this country for 14 generations and whose members shared many genes.

In this case, Dr. Pollin said, she and her colleagues traced the apoC-III mutation to a member of the Amish community who was born in the 18th century.

The gene is also regulated by insulin, noted Dr. Daniel J. Rader, a heart disease researcher at the University of Pennsylvania, and people with diabetes have high levels of APOC3, high levels of triglycerides and an increased risk of heart disease.

[suspire]

The full article: http://www.nytimes.c...art.html?ref=us

For the sake of heart disease research, 809 members of the Old Order Amish community agreed to go to a clinic in Lancaster, Pa., near their homes, and drink a rich milkshake that was made mostly of heavy cream. Over the next six hours, a group of investigators took samples of their blood, determining how much fat was churning through their bloodstreams. Most of the study participants responded as expected — their levels of triglycerides, a common form of fat in the blood, rose steadily for three to four hours and then declined. But about 5 percent had an extraordinary reaction: their triglyceride levels started out low and hardly budged.

It turns out, the researchers report in the Friday issue of the journal Science, that those individuals who barely responded have a mutation that disables one of their two copies of a gene called apoC-III. The gene codes for a protein, APOC3, that normally slows the breakdown of triglycerides.

With the mutated gene, people break down triglycerides unusually quickly. And, the investigators find, they also have low levels of LDL cholesterol, which at high levels increases heart disease risk. They have high levels of HDL cholesterol, which is associated with a decreased risk of heart disease. And they appear to have arteries relatively clear of plaque.

As for apoC-III, the study clarifies its role, said Dr. Alan R. Tall, head of the molecular medicine division at Columbia. “It was known from animal studies that apoC-III might have a role like this,” Dr. Tall said. “But the human information is really novel. We suspected it might be the case but this nails it down.”


Dr. Rader agreed. “This is among the strongest human evidence we have that APOC3 is quote, unquote, bad,” he said. “If you had a drug to turn off the gene to prevent as much APOC3 being made, this study suggests that that would be beneficial to do.” But he added that there were no such drugs on the immediate horizon.

So it seems like turning off this apoC-III gene would be a huge break-through in heart health. Definitely interesting and an indicator of how huge an impact genetics can play over all our efforts at nutrition, supplementation, etc.

I think the other thing that was interesting is the impact of the milkshake, itself. The milkshake was mostly heavy cream. I'd love to know exactly what was in the milkshake--clearly nothing the Amish would have objected to on religious grounds. There have been a lot of discussions on the boards about what's bad for you--fats, carbs, etc. Is this evidence in one direction or the other?

EDIT: Oops. Didn't realize this had been posted already.

Edited by suspire, 12 December 2008 - 05:04 PM.

[edward]

The problem with turning off an entire gene (apoC-III or any other) is that who knows what other things said gene control. Since we already have a group of people with one of the copies of the gene turned off we can study them and any issues they have. My guess is they are not "normal" in that there are other health issues that may be worse but that is just a guess.