Influence of the SstI polymorphism at the apolipoprotein C-III gene locus on the plasma low-density-lipoprotein-cholesterol response to dietary monounsaturated fat.
The plasma lipid response to changes in dietary fat and cholesterol can vary between individuals. The SstI polymorphism, arising from a cytosine to guanosine substitution in the 3' untranslated region of the APOC3 gene distinguishes between two alleles--S1 and S2. The S2 allele has been associated with elevated plasma triacylglycerol, cholesterol, and apolipoprotein (apo) C-III concentrations. In 90 young men we examined the effect of the same mutation on the response of low-density-lipoprotein (LDL) cholesterol to dietary monounsaturated fat. The frequency for the S2 allele was 0.14. Subjects were fed a low-fat diet for 25 d, followed by a diet rich in monounsaturated fatty acid (22% MUFA, 38% total fat) for 28 d; lipoproteins were measured at the end of each diet. There were no significant differences in initial total cholesterol between subjects with the APOC3*S1/APOC3*S1 (S1/S1) and APOC3*S1/APOC3*S2 (S1/S2) genotypes. After consumption of the diet high in MUFA, significant increases in LDL cholesterol (0.13 mmol/L, P < 0.027) were noted in the S1/S1 subjects whereas a significant decrease was observed in the S1/S2 subjects (-0.18 mmol/L, P < 0.046). Significant genotypic effects were seen for diet-induced changes in LDL cholesterol (P < 0.00034), total cholesterol (P < 0.009), and apo B (P < 0.0014). A study of the effect of the interaction between this mutation with that present in position -76 of the APOA1 gene promoter region (G/A) revealed that both mutations had an additive effect on changes in total cholesterol, LDL cholesterol, and apo B induced by diets. Plasma LDL-cholesterol responsiveness to the diet may be explained, at least in part, by variation at the APOC3 gene locus.
López-Miranda
J
J
Unidad de Lipidos y Arteriosclerosis, Hospital Universitario Reina Sofia, Córdoba, Spain.
Jansen
S
S
Ordovas
J M
JM
Salas
J
J
Marín
C
C
Castro
P
P
Ostos
M A
MA
Cruz
G
G
López-Segura
F
F
Blanco
A
A
Jiménez-Perepérez
J
J
Pérez-Jiménez
F
F
D000328:Adult; D000483:Alleles; D016632:Apolipoprotein A-I / Q000097:blood; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000235:genetics*; D008078:Cholesterol, LDL / Q000097:blood*; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism*; D005784:Gene Amplification; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic
D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D008078:Cholesterol, LDL; D004041:Dietary Fats