Heterozygous apolipoprotein C‐II deficiency: lipoprotein and apoprotein phenotype and Rsal restriction enzyme polymorphism in the Apo C'IIPadova kindred

Deficiency of apolipoprotein C-II (apo C-II), the cofactor for lipoprotein lipase, results in the familial chylomicronaemia syndrome characterized by severe hypertriglyceridaemia and fasting chylomicronaemia. To investigate the biochemical features of the heterozygous state for apo C-II deficiency, we characterized the lipid, lipoprotein and apolipoprotein profiles in 18 relatives of two affected individuals (brother and sister) homozygous for the apo C-IIPadova gene defect which results in the synthesis of a truncated 36 amino acid apolipoprotein. Carrier status was established in first degree relatives as well as in seven non-obligate heterozygotes by restriction enzyme analysis of amplified apo C-II genomic DNA using RsaI. No significant differences in lipid, lipoprotein and apo C-II levels were observed in heterozygotes when compared to unaffected family members. Thus, in this study, the carrier state was not associated with hypertriglyceridaemia or reduced plasma levels of apo C-II. However, analysis of amplified DNA from members of the apo C-IIPadova kindred by digestion with the enzyme RsaI, which identifies the mutant apo C-II, permitted the identification of heterozygous family members which could not be recognized by measuring either fasting triglycerides or plasma apo C-II levels. This study provides further evidence that apo C-II deficiency syndrome is a heterogeneous disease not only at the molecular level but also on the clinical ground with variable phenotypic expression in heterozygous individuals from different kindreds.