Pattern of gradient of apolipoprotein E allele *4 frequencies in western Europe.

The apolipoprotein E gene (APOE) is located on chromosome 19. The three most common APOE alleles account for most of the corresponding peptide chain variations in most human populations. APOE*3 is the most common allele, coding for the product E3; APOE*2 codes for an Arg-158-->Cys substitution (E2), and APOE*4 codes for a Cys-112-->Arg product (E4). We completed a meta-analysis of APOE allele frequencies from 30 geographically defined populations in Europe, including Iceland and Turkey. We performed a weighted multiple regression using normalized geographic coordinates and a fourth-degree polynomial. Next, we constructed maps showing isofrequencies of the *4 allele in Europe. We found a clear north to south decline in *4 allele frequency for continental Western Europe. No such clinal pattern was apparent for the *2 allele frequencies, but for *3 we found an inverse south to north decreasing gradient. Symmetry between the clines of the *4 and *3 alleles is due to a negative correlation coefficient (r = -0.89). We also plotted APOE allele frequencies against latitude; a decreasing cline was evident for *4 frequencies (y = -0.152 + 0.006x, r = 0.904) and an increasing cline was evident for *3 frequencies (y = 1.087 - 0.006x, r = 0.809). Clines for the APOE alleles could be the result of natural selection.