Wednesday, February 03, 2010

Lipoprotein(a) Oxford abstract

This is Watkins, one of the senior authors of this paper on Lp(a) and heart disease:

"This is the most convincing evidence so far that this protein [Lp(a)] is directly part of the pathway that causes heart disease rather than a bystander. If we can target it through treatment, we might expect to lower the risk of disease," coauthor Dr Hugh Watkins (University of Oxford) told heartwire.

OK, we have known for quite a long time that Lp(a) is associated with heart disease. We also know that genetics has a big influence on the level of Lp(a) in the bloodstream. The basic rule is that if you have a small number of kringle IV repeats from your apo(a) genes you will have a large amount of Lp(a) in your blood stream. All of this is old news.

How many repeats of kringle IV you have is a genetic trait. The people at Oxford have used a very sophisticated search technique to locate a couple of changes, each involving a single base pair, in the region of the DNA which makes up the chromosome area coding for apo(a). Either of them affects the number of kringle IV repeats you have in your apo(a). Hence the amount of Lp(a) in your blood.

Finding two single point DNA variations which influence kringle IV repeats is a huge achievement. We now have a piece of genetic mechanism information. What puzzles me is how this is any different from simply counting the number of kringle IV repeats in apo(a) extracted from an ordinary blood sample, which we have been doing for years, without knowing exactly which change in the DNA affected the count.

What is assumed in this paper and the inferences drawn from it is that Lp(a) is intrinsically bad and that genes are the sole control of the level of Lp(a).

Both assumptions are probably wrong. We have to back to Tanzania to see what might actually influence Lp(a) in people with identical apo(a) kringle IV repeats. Hint, its not atrovastatin or ezetimbe.

But one thing came out of the abstract which is actually quite interesting. There is an association between these gene changes, "a small Lp(a) lipoprotein size" and heart disease.

I'm just wondering if a small Lp(a) particle is also a dense Lp(a) particle..........

Back to the Bantu next.


1 comment:

Neonomide said...

I remotely know about Lp(a) from yours and Dr B Gs informative posts and cannot say more about this, but I see some resemblance to these recent news on Crohn's disease:

What really strikes me is that these researchers actually jumped their logic into actually almost recommending Vitamin D! Very uncommon, since mostly the card is "we need more research" which in my ears is the synonym for "gimme more research money":

"We have identified a new treatment avenue for people with Crohn's disease or other inflammatory bowel diseases."

I'm still recovering my pieces of jaw from my floor.

I recall you also mentioned that Crohn's may be relative to intestinal bacteria. It very well may be correct, since transmission of feces has already been a successful treatment in Colitis ulcerosa. Even in case of obesity. ^^

Sorry for a slight derailing here. Just wanted to point out some tidbits.