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. APOE3 is the most common allele, coding for the product E3; APOE2 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.