Genetic Variation in the Apolipoproteins C-II and C-III

Abstract

The C group apolipoproteins are primarily associated with triglyceriderich lipoprotein particles (1). They are important in triglyceride metabolism where they act as allosteric affectors of lipoprotein lipase. Apolipoprotein C-II is an activator of lipoprotein lipase while C-III is an inhibitor of both lipoprotein lipase and hepatic lipase. Apolipoprotein C-III may also be involved in the receptor mediated uptake of triglyceriderich lipoproteins. Genetically determined deficiency of C-II is associated with a functional deficiency of lipoprotein lipase and severe hypertriglyceridemia (2). Menzel, et al (3) have reported a protein polymorphism in APO C-II in U.S. Blacks that involved the substitution of glutamine for lysine at residue 55 of the C-II polypeptide chain. They reported a frequency of 12% for this variant in a sample of 50 normolipidemic U.S. Blacks. Sepehrnia, et al (4) confirmed the presence of this polymorphism in U.S. Blacks, demonstrated its presence in Nigerians, and verified an autosomal codominant pattern of segregation in families. Reports of genetic variation in apolipoprotein C-III are restricted to two types of rare families. One having combined apolipoprotein A-I/C-III deficiency due to a sequence inversion involving both the APO A-I and C-III genes (5). Deficient family members have abnormalities of triglyceride metabolism that are corrected by the infusion of normal C-III (6). The second variant is recognized by unusually high levels of unglycosylated APO C-III (APO C-III0) due to the replacement of threonine by alanine at position 74 of the polypetide chain, which prevents 0-glycosylation (7). The latter mutation is not assocociated with gross alteration in lipoprotein levels.