AIMILANO APOPROTEIN IDENTIFICATION OF THE COMPLETE KINDRED AND EVIDENCE OF A DOMINANT GENETIC TRANSMISSION

The AI(Milano) apoprotein variant is associated with a marked reduction of high density lipoprotein (HDL) cholesterol levels and with increased triglyceridemia. In spite of the low HDL-cholesterol (HDL-Ch), carriers do not generally show clinical signs of atherosclerosis. The biochemical disorder is linked to a molecular change in apoprotein AI, that is, an arg → cys substitution in the 173 position, thus allowing the formation of AI(Milano)-AI(Milano) dimers and AI(Milano)-AII complexes. The origin of the vatiant gene has been located in Limone sul Garda, a small community in Northern Italy (about 1,000 individuals). This community gas a genetic, biochemical, and clinical individuality, consequent to its isolation up to a few years ago; the citizens show highly uniform alimentary habits and elevated consanguinity. The complete population of the small village was sampled, and, by the use of an analytical isoelectric focusing technique for the detection of the mutant, a total of 33 living carriers, ranging in age from 2 to 81 yrs, were identified. Analysis of the genealogic tree of the complete family groups showed that the apoprotein (apo) AI(Milano) is transmitted as an autosomal dominant trait, all carriers coming from a single mating couple, living in the eighteenth century. The carriers are heterozygous for the apoprotein variant. Lipid-lipoprotein parameters of the AI(Milano) carriers were compared with the corresponding sex and age classes of the general population. A significant reduction in the HDL-Ch levels and a considerable mean increase of triglyceridemia were detected, the latter finding not reaching statistical significance because of the small number of AI(Milano)-positive individuals. These reprensent the most numerous known group of carriers of an apolipoprotein mutation and, from the clinical point of view, show an unusually low prevalence of atherosclerotic vascular conditions.