EFFECT OF 347-SERINE MUTATION IN APOPROTEIN A-IV ON PLASMA LDL CHOLESTEROL RESPONSE TO DIETARY-FAT

Lipid response to dietary fat and cholesterol is, to a large extent, g enetically controlled. Apoprotein (apo) A-IV has been related to fat a bsorption and to the activation of some of the enzymes involved in lip id metabolism One mutation has been described in the apo A-IV gene tha t causes substitution of Ser for Thr at position 347. To study the inf luence of this mutation on the plasma LDL cholesterol (LDL-C) response in diets of various fat content and fatty acid saturation, 41 healthy male subjects were studied, 25 of whom were homozygous for the Thr al lele (347Thr) and the rest who were either homozygous (n=2) or heteroz ygous carriers of the Ser allele (347Ser). They consumed three consecu tive diets, each of 4 weeks' duration: one rich in saturated fat (SFA diet: 38% fat, 20% saturated), a National Cholesterol Education Progra m (NCEP) type 1 diet (28% fat, 10% saturated), and a third rich in mon ounsaturated fat (MUFA diet; 38% fat, 22% monounsaturated). Carriers o f the 347Ser allele presented a greater decrease in total cholesterol (-0.7 vs -0.44 mmol/L, P<.034), LDL-C (-0.62 vs -0.31 mmol/L, P<.012), and apo B (-14 vs -8 mg/dL, P<.01) levels when they were switched fro m the SFA to the NCEP type 1 diet than homozygous carriers of the 347T hr allele. The change from the NCEP type 1 to the MUFA diet resulted i n a greater increase in total cholesterol (0.18 vs -0.05 mmol/L, P<.02 8) and apo B (5 vs -1 mg/dL, P<.006) levels in the 347Ser than in the 347Thr individuals. In a previous study, we demonstrated that the G--> A polymorphism at position -76 of the gene promoter of apo A-I affects the LDL-C response to dietary fat. We therefore decided to study the effect of the interaction between these mutations on this response. We found that both mutations have an additive effect on total cholestero l, LDL-C, and apo B dietary-induced changes. Our results suggest that total cholesterol and LDL-C response to dietary fat is influenced by t he 347Ser mutation of apo A-IV.