Monday, 31 March 2014

Apolipoprotein E - genealogy and picking grapes

This is part 3 of my little ApoE series. I'm making an attempt to put them in some logical order, so see parts 1, part 2 to make some sense of this one. 

The next few posts will outline some population observations, particularly in regard to E4. I realise that this sort of information can only provide clues as to what mischief your particular ApoE gets up to, but they're at least something to start with.

You may notice I don't pay equal attention to E2, which is partly for selfish reasons, but also because E2 is even rarer than E4 and the only unpleasant condition that I'm aware of that is associated with E2/E2 is something called Type 3 hyperlipoproteinemia. "Only" is probably a poor choice of word, because it's a particularly nasty condition, but it's a lot less common than something like Alzheimer's and dementia.

ApoE Geographic distribution.
In a general global sense, the different Apolipoprotein E alleles are encountered as follows: 
ApoE allele
Mean average frequency
E2
6.4%
E3
78.3%
E4
14.5%

Of course it depends on where you live and where your descendants are from. It seems that, in Europe at least, the further you travel north, the more people with E4 you will meet. 
The table above is from the ApoEurope Project and they found that the number of people with E4 near the Mediterranean (Greece, Portugal, Spain) was lower when compared with more northern populations in Ireland, Finland and France. 

E4 is also fairly prevalent in places where skin colour is naturally dark. For example: 
Population
Approximate E4 %
Central African Pygmies
40.7%
Tutsi (East Africa)
38.5%
Papuans
36.8%
Australian Aboriginals
26%

If you go digging for papers on this topic, you'll generally find that E4 is less common in certain populations and locations and while the geographical distribution is an interesting observation, it doesn't really tell us anything by itself. So we'll move on to the next observation:

Vitamin D status

People with E4 tend to have higher circulating levels of Vitamin D. Again, interesting, but what does it mean?

Well, if you are in to putting several associations together and jumping to a conclusion, and I definitely am when it suits my argument, then you may speculate that evolution had a hand in giving E4 (and therefore a smaller chance of suffering Vitamin D deficiency) to those who were less likely to get a sun tan. Or put another way, E3 evolved in those populations getting more Vitamin D while picking grapes in places like Rome or Cyprus.

The skin colour observation above, may also play a part here as people with dark skin will synthesise less Vitamin D from the sun than those with fair skin. Sound logical? Good. If it doesn't, you obviously don't belong here because I hate being contradicted.

Of course I'm kidding, I don't really gain any benefit from investing my beliefs in this relationship. While it might be a nice thing to naturally have decent Vitamin D levels, I'm a white man living in the tropics, so it's not exactly a massive bonus for me. I couldn't avoid the sun if I wanted to.

Summary

The list of ApoE observations is not exactly a short one, so these two are just a start. We're obviously dealing with a lot of associations rather than any definitive facts, but in the world of ApoE research, that is mainly what we have to go with. It is theorized by certain experts that E4 is the 'ancestral' gene and that E3 and E2 evolved over time in response to agriculture and a greater nutritional reliance on grains. Whether that is true, I doubt we'll ever find out, but I s'pose it's fun to play these guessing games.

My descendants are from Great Britain and Northern Germany, so I loosely fit the typical E4 profile detailed in this post, but that's not really useful in understanding how Mrs Evolution thinks I should be living my life to maximise health and longevity in a modern society. 

Which is the whole point of researching this topic.

Trust me, the story gets more interesting. More to come. 

References:
Eisenberg et al - Worldwide Allele Frequencies of the Human Apolipoprotein E Gene: Climate, Local Adaptations, and Evolutionary History 2010
Haddy et al, The importance of plasma apolipoprotein E concentration in addition to its common polymorphism on inter-individual variation in lipid levels: results from Apo Europe, 2002.
Schiele et al, Apolipoprotein E serum concentration and polymorphism in six European countries: the ApoEurope Project, 1999.
Huebbe et al, APOE 4 is associated with higher vitamin D levels in targeted replacement mice and humans, 2011.
Hollick and Chen, Vitamin D deficiency: a worldwide problem with health consequences, 2008.





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