Effect of 360His mutation in apolipoprotein A-IV on plasma HDL-cholesterol response to dietary fat.
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.
Jansen
S
S
Lipid Research Unit, University Hospital Reina Sofia, University of Cordoba Medical School, Spain.
Lopez-Miranda
J
J
Ordovas
J M
JM
Zambrana
J L
JL
Marin
C
C
Ostos
M A
MA
Castro
P
P
McPherson
R
R
Lopez Segura
F
F
Blanco
A
A
Jimenez Pereperez
J A
JA
Perez-Jimenez
F
F
D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood; D001054:Apolipoproteins A / Q000097:blood / Q000235:genetics*; D002352:Carrier Proteins / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D018752:Diet, Fat-Restricted; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage*; D004734:Energy Metabolism; D005227:Fatty Acids / Q000097:blood; D005229:Fatty Acids, Monounsaturated / Q000097:blood; D005838:Genotype; D006023:Glycoproteins; D006639:Histidine / Q000235:genetics; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D009154:Mutation / Q000235:genetics
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D006023:Glycoproteins; D008055:Lipids; C022205:apolipoprotein A-IV; D006639:Histidine