Effects of Dehydroepiandrosterone-sulfate on the Apo E Genotype Influence on Plasma Lipid Levels in Prepubertal Children

Gender differences in the apolipoprotein (apo) E genotype effect on plasma lipid levels reported in adults have also been found in pre-pubertal children. In adults, the difference seems to be due to the influence of sexual hormones. The reason why this difference exits between pre-pubertal girls and boys, for whom those sexual hormones are not different, is unclear. However, there is an important difference in Dehydroepiandrosterone-sulfate (DHEA-S) levels between pre-pubertal boys and girls. To evaluate the influence of DHEA-S on apo E genetic determinants of plasma lipids levels in pre-pubertal children we measured plasma DHEA-S in 1045 healthy children (534 males and 511 females) 6 to 8 years old in which a different apoE influence on lipid levels had been reported between girls and boys. Our observations demonstrate that the extent of the lipid increasing or decreasing effects associated with each allele were modulated by DHEA-S. DHEA-S increases the hypolipemic effect of the ε2 allele and decreases the hyperlipemic effect of the ε4 allele. In conclusion, the interaction of apo E genotype and DHEA-S may represent a critical determinant of TC, LDL-C and apo B levels in children at the prepuberal age.