Numerous molecular variants of the
protein moiety of human
circulating lipoproteins ("
apolipoproteins" or "
apoproteins") have been described in recent years. Molecular alterations of
apolipoproteins may lead to an impaired
lipid binding and/or to an accelerated or delayed
lipoprotein catabolism. Many variants, particularly those of the E
apoprotein system, are associated with premature
atherosclerosis. In the case of the
Apo AI variants, the concomitant deficiency of
Apo AI and Apo CIII leads to severe clinical
atherosclerosis. Conversely, molecular variants of
Apo AI (several of which come from FRG, i.e. AI-Marburg, -Giessen, -Münster) do not go together with significant clinical abnormalities. The case is different for
Tangier disease, characterized by the complete absence of
high density lipoproteins, where a dramatic tissue
lipid deposition may occur. One molecular variant,
Apo AI-Milano, while leading to a significant reduction of HDL, does not seem to be associated with clinical
atherosclerosis, but rather with a protection from the disease. The presence of major
apolipoprotein abnormalities in familial groups of variable size, provides a molecular explanation for some significant alterations of lipid metabolism. Moreover, it offers, to clinical and basic studies, a useful model for the understanding of the function and metabolism of human
apolipoproteins.