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 +/-) polym orphisms at the APOA1 gene locus for associations with plasma lipid le vels and response to an NCEP-I diet in 69 (44 women, 25 men) heterozyg otes for familial hypercholesterolemia (FH). Subjects were studied at baseline (after consuming for one month a diet with 35% fat, 10% satur ated, and 300 mg/day cholesterol) and after 3 months of an NCEP-I diet . No gender-related differences for any of the lipid variables examine d were found and the data were analyzed for men and women combined. Fo r the apo AI - 75 (G/A) polymorphism, there were 51 G/G and 18 G/A sub jects. At baseline, G/A subjects showed significantly lower total chol esterol (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, triglyc erides and VLDL-C values. Following the NCEP-I diet these genotype-rel ated differences remained significant for total and LDL-C. The MspI (- ) allele at the apo AI + 83 polymorphism was detected in the heterozyg ous state in five subjects and its presence was not associated with al tered baseline lipids nor with dietary response to the NCEP-I diet. Ou r results suggest that FH subjects carrying the A allele at the apoAI - 75 (G/A) polymorphism have significantly lower total and LDL-C and a po B baseline levels but respond to a low-fat diet with similar reduct ions in total and LDL-C when compared with homozygotes for the G allel e at this polymorphic site. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.