ApoE4 – The Ancestral Allele

For ApoE4 carriers interested in primal diets and science

Food collection, not production

with 5 comments

Apolipoprotein E (APOE) allele distribution in the world. Is APOE*4 a `thrifty’ allele?
R. M. CORBO and R. SCACCHI Department of Genetics and Molecular Biology, University `La Sapienza, Rome.  CNR Center of Evolutionary Genetics, Rome

Summary begins:

Apolipoprotein E (APOE¯gene, apoE¯protein) plays a central role in plasma lipoprotein metabolism and in lipid transport within tissues. The APOE shows a genetic polymorphism determined by three common alleles, APOE*2, APOE*3, APOE*4 and the product of the three alleles differs in several functional properties. APOE is involved in the development of certain pathological conditions. In particular, the APOE*4 allele is a risk factor for susceptibility to coronary artery disease (CAD) and Alzheimer’s Disease (AD). In the present study we analyzed the APOE allele distribution in the world…

Some key messages:

It appears from our analysis that the APOE*3 allele is the most frequent in all the human populations and that its frequency is always negatively correlated with that of APOE*4, indicating that the ancestral allele was progressively substituted by the new allele carrying the 112arg!cys mutation. The highest APOE*3 frequencies are found in populations with a long-established agricultural economy (Gerdes et al. 1996) such as those of the Mediterranean basin (0.849±0.898) or East Asia (0.82±0.87). It is possible that the metabolic properties of the E3 isoform proved to be particularly advantageous in the transition from food collection to food production. At present, the frequency of APOE*4 within all the major human groups remains higher in those populations…where an economy of foraging still exists, or food supply is now or has until recently been scarce, sporadically available or qualitatively poor. Under these environmental conditions, carrying the APOE*4 could be still useful. For example, most of these populations have lower plasma cholesterol levels than those observed among Western countries. Since APOE*4 is associated with both a higher absorption of cholesterol at intestinal level, and higher plasma cholesterol levels, individuals carrying it would be favoured because this allele could help in rebalancing cholesterol levels which would otherwise be too low (Scacchi et al. 1997)

Hopefully this just means we should eat primal, I totally don’t want to eat a low cholesterol diet.  As we can see below, it’s clearly a gene-environment interaction that leads to high levels of heart disease (CAD) and Alzheimer’s (AD) for APOE4s, because the developing world has more E4s yet far less CAD & AD.  There are two hypothesis for what the environmental aspect of the Western lifestyle is which triggers these problems, one of which is good for us & one is bad.

The first is that it’s the Western diet & low-activity lifestyle, which means by eating primal, we’ll be fine.  The second is that since CAD & AD happen when old, it may just be that longer Western lifespans allow the disadvantages of E4 to develop.  The key data for us, then, is to find some high E4 populations, and see what their lifespans are & whether those individuals who live into their 70s & 80s get CAD & AD.

APOE*4 could be considered a `thrifty’ allele based on certain functional properties it exhibits and on its distribution among human populations. At present it is considered a susceptibility factor for CAD and AD, diseases highly prevalent in Western populations but far less so or completely absent in developing countries, where instead APOE*4 is most frequent. Since both CAD and AD are complex diseases whose occurence depends on gene-environment interactions, exposure of APOE*4 to contemporary environmental conditions may have rendered it a susceptibility allele for CAD and AD. One of the new environmental conditions favouring this change could be the western lifestyle in general, with its diets rich in carbohydrate and fat, but poor in fibre intake, along with reduced physical activity. Longer average lifespans and aging populations count as two more environmental factors particular to the developed countries, since both the diseases occur in adult and advanced age.


Written by patrissimo

December 29, 2011 at 5:03 am

5 Responses

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  1. Keep writing these; they’re good. I think I’m apoE4 x 1 based on a very exaggerated LDL response to SFAs.

    Dan H

    October 27, 2012 at 3:56 am

  2. An interesting paper released recently: http://www.ncbi.nlm.nih.gov/pubmed/23112842

    “CONCLUSIONS: We found no coding variation within and between chimpanzee populations, suggesting that the maintenance of functionally diverse APOE polymorphisms is a unique feature of human evolution.”

    St Nick

    November 13, 2012 at 10:34 pm

  3. Very cool blog hope you continue to post.


    January 3, 2013 at 8:44 pm

    • I can’t be on statins due to muscle pain. I am on Gemfibrozil now. I haven’t had lab done yet. Are most of your doctors recommending the mediterannean diet or just a low fat diet, with exercise, weight lifting and losing weight. Do you have something else you are doing that is giving you better labs? I am a APO E 3/4


      February 26, 2013 at 4:06 am

  4. I used the DNA analysis from 23andme.com. It verified that, yes, I am apoE4 x 1. I have been compiling research links and notes on apoE4 and Alzheimer’s. I will put what I’ve got so far up on my wordpress blog (resolvingthecontroversies) soon and continue to update it as I collect more.

    Dan Hunter

    February 6, 2013 at 1:03 pm

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