A variation in the apolipoprotein C-III gene is associated with an increased number of circulating VLDL and IDL particles in familial combined hyperlipidemia.

Detailed plasma lipoprotein analyses were con- ducted on 16 familial combined hyperlipidemic (FCHL) pro- bands, all their available family members (n = 106) together with 12 normolipidemic control families (n = 63), and the results were assessed in relation to a C,,,-T polymorphism in exon 3 of the apoC-I11 gene. The frequency of the TI,, geno- type (CT + TT) was significantly elevated in the probands relative to control subjects (0.64 vs. 0.36; P < 0.01) and was associated with elevated concentrations of plasma triglyceride (P < 0.02) and apoC-I11 (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 TllW genotype was also associated with elevations in VLDLapoB (P < 0.005) and IDLapoB (P < 0.04) indicating a relationship between this variation and an increased number of triglyceride-rich particles. These findings were confined to the hyperlipidemic members of the FCHL families and showed a strong geno- type-status interaction (P < O.OOl).l It is of considerable clinical relevance that the apoC-111 gene may be acting as a modifier gene that is only expressed in the presence of other factors (e.g., increased VLDL flux, low LPL activity) and there- fore may predispose those members of FCHL families car- rying the TllW allele to express the FCHL phenotype.-Ri- balta, J., A. E. La Vie, J. C. Vake, S. Humphries, P. R. Turner, and L. Masma. A variation in the apolipoprotein G I11 gene is associated with an increased number of circulating VLDL and IDL particles in familial combined hyperlipidemia. J. Lipid RES. 1997. 38: 1061-1069.