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A Track Your Plaque practical guide to Apoprotein E
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How it may affect diet, drug, and supplement decisions


What? Another test?
Apoprotein E (apo E) is a test for the more advanced Track Your Plaque follower. It is definitely not part of the starting effort, since most people do just fine without knowledge of their apo E gene status.
So why bother?
Because there are occasional people, likely no more than 10-20%, who have unexpected responses to diets, supplements, and other treatments that defy normal “rules.” For instance, you take high-dose fish oil for reduction of lipoprotein(a). In most people, this results in a slow, long-term reduction in lipoprotein(a) without distorting other measures substantially. But a few percent of people who use high-dose fish oil experience marked increase in total LDL particle number, apoprotein B, or LDL cholesterol; increased triglycerides; even increased small LDL. This is a situation in which knowledge of apo E status can be helpful.
Admittedly, we are venturing off into rather thin air here: Fewer than 2% of all physicians even know what apo E is, let alone understand what it means. As is often the case with obtaining other lipoprotein measures, you will have to either ask your healthcare provider to order an apoprotein E genotype test with your blood work or use one of the several services that provide direct-to-consumer testing.
Apo E can also be a measure to consider to fine-tune your program, e.g., increasing heart scan score despite your best effort.
What is Apo E?

As with other genetic traits, every human has two apo E genes: one from mom and one from dad. They can be two of the same 

gene or they can be two different genes.
Over the years, numerous minor variations on the apo E gene have been identified, but their real-life behavior has caused them to grouped into three general designations: apo E2, apo E3, and apo E4.
The gene for apo E3 is the most common; approximately 60% of people have two genes for apo E3, i.e., apo E 3/3. Apo E4 is the next most common, with 20% of Americans having one apo E4, while an additional 5% have two, i.e., apo E 4/4. Apo E2 is the least common, with 10% of Americans having one apo E2, only 1% having two, i.e., apo E 2/2. Also rare is apo E 2/4 (Mahley 2000).
The product of the apo E gene, apoprotein E (all types), is responsible for directing the fate of postprandial (after-eating) lipoproteins like chylomicrons, chylomicron remnants, and VLDL. Postprandial particles that contain apo E are recognized by the liver for uptake and processing. HDL also contains apo E, although it appears to not have as important as role as with postprandial lipoproteins.
Apo E2 closely resembles apo E3 except for 2 amino acids. That small difference causes it to bind weakly (1/100th the binding power of apo E3) to the liver receptor. This means that chylomicron remnants and VLDL—all the postprandial byproducts of your last meal—fail to be taken up by the liver when one or two apo E2 genes are present (Mahley 2000). It means that people with apo E2, especially E2/2, can accumulate postprandial lipoproteins, like chylomicrons, chylomicron remnants, and VLDL, often suggested by high triglyceride and low HDL levels. The expression of the high VLDL/triglyceride, low HDL pattern is especially marked when metabolic syndrome is present, i.e., central obesity and associated features. Despite the accumulation of postprandial lipoproteins, LDL measures like LDL particle number, apoprotein B, and even calculated LDL tend to be slightly lower (<10%) in people with one apo E2, more so (25%) in people with apo E2/2 (Schaefer 1994).
Some people with apo E 2/2, especially if overweight with insulin resistance (metabolic syndrome), can develop the full-blown form of much delayed postprandial clearance of lipoproteins, expressed as “type III hyperlipidemia” or “familial dysbetalipoproteinemia” characterized by high triglycerides (usually 250 mg/dl or greater) and VLDL (Zhao 1994). Despite the increased VLDL that could potentially be converted to LDL, there appears to be impaired conversion to LDL (Zhao 1994).
In contrast, apo E4 is more strongly bound by the liver receptor for postprandial byproducts than apo E3. It means that all the byproducts of your last meal, from chylomicron remnants on down, are cleared more effectively than in people with apo E2 or E4. So what’s the problem with apo E4?
Although postprandial lipoproteins are cleared more effectively with Apo E4, there is a corresponding increased absorption of dietary cholesterol and failure to clear LDL particles from the bloodstream (Mamotte 1999). VLDL particles are also more efficiently converted to LDL particles (Welty 2000). This leads to an increase of all LDL measures: LDL cholesterol, LDL particle number, apoprotein B. These values in both apo E4/3 and apo E 4/4 tend to be higher than in people with E3 or E2, though usually by <10% (Schaeffer 1994).
What do we know about Apo E?

No doubt: Apo E can introduce a frustrating tangle of effects that can often make our jobs more difficult, rather than making it easier.
Nonetheless, a number of important observations have been made about apo E over the past 30 years: 

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