Influence of genetic variation at the apo A-I gene locus on lipid levels and response to diet in familial hypercholesterolemia Original Research Article

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.