Gender-specific effects of apolipoprotein E genotype on plasma lipid levels in a population-based sample of 6-7-year-old children in Spain.

AIM: The effects of gender on the association between apolipoprotein E genotype and plasma lipid levels remain unclear in children. The aim of the present work was to evaluate these gender differences in a large population-based sample of 6-7-y-old children, free of the effects of sex hormones. METHODS: Lipid levels and apo E genotypes were studied in a sample of 1255 (631 M, 624 F) Caucasian schoolchildren, aged 6-7 (mean age, 6.7) y in Spain. RESULTS: A significant effect of the apo E genotype on plasma total cholesterol, LDL-C (low-density lipoprotein cholesterol) and apo B levels was observed. Taking the homozygous epsilon3epsilon3 genotype as reference, the presence of the epsilon2 and epsilon4 alleles is associated with substantially lower and higher plasma levels, respectively, of these variables. It was found that the effect of the apo E polymorphism on total cholesterol, LDL-C and particularly on apo B levels was greater in girls than in boys. CONCLUSION: At this prepubertal age, the influence of the apo E genotype on total cholesterol, LDL-C and apo B levels is more evident in girls than in boys. This difference in effect is not due to sex hormones. In our opinion, the earlier increase in adrenal androgens in girls than in boys at this age related to pubertal maturation could be responsible for these differences.

Association between the TaqIB polymorphism in the cholesteryl ester transfer protein gene locus and plasma lipoprotein levels in familial hypercholesterolemia.

Cholesteryl ester transfer protein (CETP) facilitates the exchange of triglycerides (TG) and cholesteryl ester between lipoprotein particles. Subjects with familial hypercholesterolemia (FH) have been reported to have higher CETP activities, which could contribute to the lower high-density lipoprotein-cholesterol (HDL-C) levels and increased cardiovascular risk observed in some of these patients. Several polymorphisms have been reported in the CETP locus; the common TaqlB polymorphism is associated, in normolipidemic subjects, with decreased CETP activity and levels and with increased HDL-C levels. No data is available on the influence of this polymorphism in FH subjects. We have examined the TaqIB polymorphism in a group of 101 FH heterozygotes from Valencia, Spain. We have observed a frequency of 0.43 for the B2 allele, similar to those reported in the general population. Based on analysis of variance (ANOVA), we found significant associations between the presence of the B2 allele and increased plasma HDL-C (P <.04) and apolipoprotein A-I (apoA-I) levels (P <.01). An opposite association was observed for low-density lipoprotein-cholesterol (LDL-C) levels, with the B2/B2 subjects having lower levels than B1/B1 and B1/B2 subjects. The plasma apoB levels followed the same trend as those for LDL-C. In addition, the response to a National Cholesterol Education Program (NCEP)-I diet was studied in 77 of these subjects. The TaqlB polymorphism did not have a significant effect over the individual dietary response for any of the variables examined, as demonstrated by the lack of significant gene by diet interactions. In summary, the CETP TaqlB polymorphism is associated with a less atherogenic lipid profile, consisting of lower LDL-C, higher HDL-C levels, and a lower LDL-C/HDL-C ratio in heterozygous FH subjects. Moreover, the B2 allele was associated with a lower appearance of arcus cornealis, xanthomata, and clinical arteriosclerotic disease in these subjects.