Apolipoprotein A-IV-2 allele: Association of its worldwide distribution with adult persistence of lactase and speculation on its function and origin

Apolipoprotein A-IV (apo A-IV) is a 46-Kd plasma glycoprotein that may play a major role in intestinal lipid absorption. A genetic polymorphism in the apo A-IV gene, apo A-IV-2, encodes a His-->Gln substitution at codon 360 t hat alters the biological function of this apolipoprotein. As the worldwide distribution of the apo A-IV-2 allele appeared similar to the frequency of a genetic polymorphism that determines the persistence of lactase into adu lthood, we examined the relationship between the apo A-IV-2 and lactase per sistence polymorphisms by compiling the prevalence of adult lactase persist ence in all populations in which the frequency of the apo A-IV-2 allele has been determined. Across 29 groups, there was an extremely strong correlati on (r = 0.937, P < 0.000001) between apo A-IV-2 allele frequency and the pr evalence of adult lactase persistence. Apo A-IV-2 allele frequency was high est in Iceland, an ancient Viking colony, and decreased across Europe in a north-to-south and west-to-east gradient, generally following hypothetical isoclines for the lactase persistence gene. There were no correlations betw een the population frequencies of the apo E2, E3, or E4 alleles and either the prevalence of lactase persistence or the frequency of the apo A-IV-2 al lele. In light of the effects of the apo A-IV-2 polymorphism on lipid metab olism, we speculate that the apo A-IV-2 allele may have originated in ancie nt Scandinavia, spread by conferring a nutritional advantage in the setting of a Lifelong high milkfat intake, and was later carried southwards by the Viking incursions into Europe. Genet. Epidemiol. 17:285-297, 1999. (C) 199 9 Wiley-Liss, Inc.