APOA-IV PHENOTYPE AFFECTS DIET-INDUCED PLASMA LDL CHOLESTEROL-LOWERING

The National Cholesterol Education Program (NCEP) recommends that dietary total fat, saturated fat, and cholesterol intake be reduced to less than or equal to 30% of calories, <10% of calories, and <300 mg/d, respectively (step 1 diet), in the general population to reduce plasma low-density lipoprotein cholesterol (LDL-C) levels and heart disease risk. We examined the LDL-C-lowering response to such a diet (26% fat, 8% saturated fat, and 201 mg/d cholesterol) compared with an average American diet (39% fat, 15% saturated fat, and 435 mg cholesterol/d) in 153 subjects using diet periods of 4 through 24 weeks for each diet phase. The mean LDL-C reduction was 13% in men (n=93) and 7% in postmenopausal women (n=60). The effect of apolipoprotein (ape) A-IV phenotype on responsiveness was examined. LDL-C lowering in men was significantly (P<.005) less (7%) for 17 apoA-IV (1/2) subjects than for 76 apoA-IV (1/1) subjects (16%). In women, 7% lowering was observed in both 12 apoA-IV (1/2) subjects and 48 apoA-IV (1/1) subjects. ApoA-IV phenotype had a significant effect on plasma high-density lipoprotein cholesterol levels during both dietary periods; women carrying the apoA-IV-2 allele had higher levels than those homozygous for the apoA-IV-1 allele. The opposite was true for triglyceride levels, but only during the period when the subjects consumed the high-fat, high-cholesterol diet. These data indicated that apoA-IV phenotype modulates the LDL-C-lowering response to a diet meeting NCEP step 1 criteria in men and that high-density lipoprotein cholesterol and triglyceride levels are affected by this locus in women.