Relationship between lipoprotein abnormalities in childhood and the risk for atherosclerotic coronary heart disease in adulthood(Comparison of the effects of genetic and environmental factors on dyslipidemia between children and adults)

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1.Acyl-CoA : cholesterol acyltransferase(ACAT)plays important roles in cellular cholesterol homeostasis.Two isoforms of ACAT have been reported(ACAT-1 and ACAT-2).An ACAT inhibitor was shown to have a lipid-lowering effect.The present study was carried out to clarify the relationship between ACAT-1 gene variants and hyperlipidemia.A missense variant(R526G), and a variant in the 5' untranslated region(-77G-.A) were identified.R526G variant did not affect plasma concentrations of lipids or apolipoproteins in subjects studied. However, among hyperlipidemic subjects, plasma concentrations of HDL-C and apoA-I in subjects with -77G-'A variant were significantly higher than those in subjects without variant.These data suggest that the intracellular PC concentration might modulate plasma HDL concentrations.2.Small LDL particles are more atherogenic than larger LDL particles.To help prevent atherosclerotic coronary heart diseases(ACHD), it may be useful to understand risk factors during childhood. We evaluated LDL-size and its relation tQ other risk factors for ACHD.LDL-size was measured by gradient gel electrophoresis in 586 children.Pattern B(LDL-size < 25.5 nm)was found in 10.8 % of boys and 4.4 % of girls.Children with pattern B had a higher body mass index (BMI) and insulin resistance, and a more atherogenic lipoprotein profile than those with pattern A (LDL-size> 25.5 nm).BMI, insulin resistance and plasma concentrations of TG, glucose and insulin decreased and plasma concentrations of HDL-C and apoA-I increased as LDL-size increased.HDL-C and insulin in boys, and BMI, HDL-C and apoA-I in girls predicted 22.9 % and 28.1 % of the variability of LDL-size, respectively.Although the contribution Qf these parameters to LDL-size in children was less than that in adults, improvement of these parameters by changes in lifestyle might be important for preventing the development of atherosclerosis, even in children.