A VARIATION IN THE APOLIPOPROTEIN C-III GENE IS ASSOCIATED WITH AN INCREASED NUMBER OF CIRCULATING VLDL AND IDL PARTICLES IN FAMILIAR COMBINED HYPERLIPIDEMIA

Detailed plasma lipoprotein analyses were conducted on 16 familial com bined hyperlipidemic (FCHL) probands, all their available family membe rs (n = 106) together with 12 normolipidemic control families (n = 63) , and :he results were assessed in relation to a C-1100-T polymorphism in exon 3 of the apoC-III gene. The frequency of the T-1100 genotype (CT + TT) was significantly elevated in the probands relative to contr ol subjects (0.64 vs. 0.36; P < 0.01) and was associated with elevated concentrations of plasma triglyceride (P < 0.02) and apoC-III (P < 0. 03), VLDL cholesterol (P < 0.005), VLDL triglyceride (P < 0.009), IDL cholesterol (P < 0.01), and IDL triglyceride (P < 0.007). The T-1100 g enotype was also associated with elevations in VLDL-apoB (P < 0.005) a nd IDL-apoB (P < 0.04) indicating a relationship between this variatio n and an increased number of triglyceride-rich particles. These findin gs were confined to the hyperlipidemic members of the FCHL families an d showed a strong genotype-status interaction (P < 0.001). It is of co nsiderable clinical relevance that the apoC-III gene may be acting as a modifier gene that is only expressed in the presence of other factor s (e.g., increased VLDL flux, low LPL activity) and therefore may pred ispose those members of FCHL families carrying the T-1100 allele to ex press the FCHL phenotype.