APOC3 Rare Variants and Lower Triglycerides, Higher HDL

[circular]

From NEJM Watch:

Genetic Studies Help Unravel the Triglyceride Problem
By Larry Husten
Edited by Susan Sadoughi, MD, and Lorenzo Di Francesco, MD, FACP, FHM
Rare variations in a gene (APOC3) that encodes for apolipoprotein C3 are associated with reduced triglyceride levels and, in turn, lower risk for heart disease, according to two studies in the New England Journal of Medicine.

In the first, researchers sequenced the genes of some 3700 people and identified several rare loss-of-function variants of APOC3. As expected, people with the variants had significantly lower triglyceride levels. They then analyzed data from more than 110,000 participants in 14 studies and observed that people with the same loss-of-function mutations had a 40% lower risk for coronary heart disease. The results, they write, "show that loss of APOC3 function confers protection against clinical coronary heart disease," though they were unable to identify a primary mechanism linking APOC3 to heart disease.

The second study included over 75,000 participants in two large Danish prospective studies. People with APOC3 loss-of-function mutations had triglyceride levels reduced by 44%, with corresponding risk reductions of 41% for ischemic vascular disease and 36% for ischemic heart disease.

In both studies, the APOC3 mutations were also linked to elevated HDL levels and other changes in lipid values. The authors of both papers write that their findings suggest that APOC3 might make for an attractive drug target.

http://www.nejm.org/doi/full/10.1056/NE ... ?query=pfw
http://www.nejm.org/doi/full/10.1056/NE ... ?query=pfw

[Julie G]

Looking for some SNPs...

[circular]

I know, I hate it when they don't provide the info we need to check. Seems like a conspiracy against power to the patients to me!

[Julie G]

I hear you.

I've pretty easily located one SNP: R19X, rs76353203. The protective allele appears to be T. Unfortunately, the older 23andMe chip doesn't report on it

I'm working on the other SNPs...Where's J1 1 when you need him?

[KatieS]

Julie, 23andme now reports on this gene as they had data for my mom (CC) who submitted her salvia in April, but not my from October. My mom strikes out on all the tests, even worse than me!

[Sandraz]

Can you guys tells me how 23&me works now? If I were to order the $99test would I get the kind of info you have from doing test earlier? What did the FDA have 23&me stop doing last fall?

Thanks,
Sandra Z

[Julie G]

I believe (please correct me if I'm wrong!) that they would run your next test on the new chip. You would still have full access to your raw data.

[Sandraz]

Is it the raw data that then goes to Prometheus.com? How does that work?
Sandra

[Julie G]

Yes, for a nominal fee you can easily do that. You simply download your raw data & they process it for you: http://www.snpedia.com/index.php/Promethease

If you've not done it before, you can also do it with your current raw data. It offers more information than the standard 23andMe health report. Even if you have done it before, I've heard the newer Promethease report is much improved. (Mine is almost 2 years old.) Be emotionally ready for a whammy. I've heard one geneticist say that "weaknesses" on one gene tend to lead to others on the same gene. I don't look good on paper

[Sandraz]

Thanks Julie!
I have no raw data bc I have not used 23&me before. I thought I would have my husband tested, then maybe my two children. Although I know they have one e4 maybe my husband has an e2 to neutralize....(I can always hope).
Then maybe me, although I don't think I want to know much more about me. unless it is good news that is. But I know that isn't the way it works...

Sandra