Influence of genetic variation at the apo A-I gene locus on lipid levels and response to diet in familial hypercholesterolemia.
We have examined the apo AI - 75 (G/A) and apo AI + 83(MspI +/-) polymorphisms at the APOA1 gene locus for associations with plasma lipid levels and response to an NCEP-I diet in 69 (44 women, 25 men) heterozygotes for familial hypercholesterolemia (FH). Subjects were studied at baseline (after consuming for one month a diet with 35%, fat, 10% saturated, and 300 mg/day cholesterol) and after 3 months of an NCEP-I diet. No gender-related differences for any of the lipid variables examined were found and the data were analyzed for men and women combined. For the apo AI - 75 (G/A) polymorphism, there were 51 G/G and 18 G/A subjects. At baseline, G/A subjects showed significantly lower total cholesterol (p = 0.0036), and LDL-C (p = 0.0023), and apo B (p = 0.0209), than G/G individuals, but no differences were found for HDL-C, triglycerides and VLDL-C values. Following the NCEP-I diet these genotype-related differences remained significant for total and LDL-C. The MspI (-) allele at the apo AI + 83 polymorphism was detected in the heterozygous state in five subjects and its presence was not associated with altered baseline lipids nor with dietary response to the NCEP-I diet. Our results suggest that FH subjects carrying the A allele at the apoAI - 75 (G/A) polymorphism have significantly lower total and LDL-C and apo B baseline levels but respond to a low-fat diet with similar reductions in total and LDL-C when compared with homozygotes for the G allele at this polymorphic site.
Department of Medicine, Hospital Clinico, University of Valencia, Spain.
R F
RF
Carmena-Ramon
J M
JM
Ordovas
J F
JF
Ascaso
J
J
Real
M A
MA
Priego
R
R
Carmena
D000328:Adult; D000483:Alleles; D016632:Apolipoprotein A-I / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D004032:Diet; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D008055:Lipids / Q000097:blood*; D008297:Male; D011110:Polymorphism, Genetic
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D008055:Lipids