Journal of Lipid Research, Vol 38, 1995-2002, Copyright © 1997 by Lipid Research, Inc.

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Effect of 360His mutation in apolipoprotein A-IV on plasma HDL- cholesterol response to dietary fat

S Jansen, J Lopez-Miranda, JM Ordovas, JL Zambrana, C Marin, MA Ostos, P Castro, R McPherson, F Lopez Segura, A Blanco, JA Jimenez Pereperez and F Perez- Jimenez
Lipid Research Unit, University Hospital Reina Sofia, University of Cordoba Medical School, Spain.

In order to determine whether genetic variability of apolipoprotein (apo) A-IV is responsible for the improvement in lipid profile when dietary saturated fats are replaced by carbohydrates or monounsaturated fats, 41 healthy male subjects were studied: 33 were homozygous for the 360Gln allele and 8 were heterozygote carriers of the 360His allele. These were administered three consecutive 4-week diets. The first was a diet rich in saturated fat (SAT diet, with 38% fat, 20% saturated. This was followed by a low fat diet (NCEP-I, with < 30% fat, < 10% saturated). The final diet was rich in monounsaturated fat (MUFA diet, with 38% fat, 22% monounsaturated). There was no difference in plasma lipid and apolipoprotein levels of both groups of individuals after consuming the SAT diet. Switching from this diet to the NCEP-I diet, carriers of the 360His allele presented a greater decrease in high density lipoprotein-cholesterol (HDL-C) (-10 vs. -1 mg/dL, P < 0.004) and apoA-I levels (-19 vs. -8 mg/dL, P < 0.037). Similarly, replacement of carbohydrates by monounsaturated fats produced a greater increase in HDL-C (9 vs. 1 mg/dL, P < 0.003) and apoA-I levels (9 vs. 2 mg/dL, P < 0.036) in carriers of the 360His mutation. Lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities and apoA-IV levels were also measured. However, no genotype- related differences were observed for these parameters. Our results suggest that variability in HDL-C and apoA-I response to diet is, at least partially, determined by the 360His mutation of apoA-IV.
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