A variation in the apolipoprotein C-III gene is associated with an increased number of circulating VLDL and IDL particles in familial combined hyperlipidemia
Journal of Lipid Research(1997)
摘要
Detailed plasma lipoprotein analyses were conducted on 16 familial combined hyperlipidemic (FCHL) probands, all their available family members (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 control 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 genotype was also associated with elevations in VLDL-apoB (P < 0.005) and IDL-apoB (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 genotype-status interaction (P < 0.001). It is of considerable clinical relevance that the apoC-III 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 therefore may predispose those members of FCHL families carrying the T-1100 allele to express the FCHL phenotype.
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关键词
remnant particles,CAD,genotype-status interaction,metabolic syndrome,A-I-CIII-A-IV gene cluster,genetic marker,predisposition
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