Worldwide Distribution of Apolipoprotein E Gene Alleles: is APOE*e4 Allele a Factor of Adaptation to Climate in Humans?

Abstract

Human APOE gene is located in 19ql3.2 region of the human genome. The gene codes for a protein called apolipoprotein E. The protein involved in lipid metabolism, regulation of blood cholesterol level and some other important cell functions. Allele’s e2, e3, and e4 are the most spread in humans. Level of cholesterol is the highest in e4 allele carriers, medium for e3 and the lowest for e2 carriers. The high cholesterol level associated with e4 allele is a risk factor for cardiovascular diseases and Alzheimer disease in westernized societies but not in African hunter-gatherers. We have established APOE allele frequencies in Iranians and Pamir population as well as in some populations of Russia (Russians, Ukrainians and Byelorussians). E3 allele and e3/e3 genotype were found the most spread in all of the populations with frequencies 0.74-0.80 and 0.60-0.64 correspondingly. We also screened for available information on APOE allele frequencies and found the data for 144 populations from different parts of the world. We have found that АРОЕ *е4 allele frequencies have a latitudinal distribution in all parts of the world. Minimum e4 frequency (3-5%) as well as maximum e3 frequency (>90%) was found in populations inhabiting areas at the latitude that corresponds to the Northern tropic. The e4 allele frequencies are growing rather symmetrically both to the north and to the south from the latitude. Spearman`s correlation coefficient between the e4 allele frequency and the latitude is high and valid both for populations to the north from the tropic (rho=0.67, P< 0.001) and for populations to the south from the tropic (rho =0.46, p0.001). For each 200 of latitude the frequency is going 10% up for the northern populations and 20% up for the southern populations. The latitudinal distribution of e3 allele frequencies is a mirror distribution for e4 frequency. Spearman`s correlation coefficient is both high and valid for the northern populations (rho=0.66, P< 0.001) and for the southern populations (rho= 0.45, P< 0.00I). The latitudinal distribution is absent for e2 allele frequencies. The e4 frequencies are closer to each other for populations inhabiting the same latitude. The same is true for e3 allele frequencies. The phenomenon can be seen even for populations of the same latitude inhabiting different continents. That means that the distribution does not reflect a trace of human migrations. We believe that both APOE* e4 and e3 alleles, but not el allele, may be associated with adaptation of humans to climate conditions.