ApoE4 Determines the Reduction in LDL-C After GH Replacement Therapy in Children With an Idiopathic GH Deficiency.

Abstract

GH activates the expression of low-density lipoprotein (LDL) receptors, leading to decreased LDL-cholesterol (LDL-C). Apolipoprotein (apo) E4 carriers suppress LDL receptor expression, rendering high LDL-C concentrations. We examined whether GH-deficient children carrying apoE4 exhibited a greater reduction in LDL-C after GH replacement therapy. We determined lipoprotein profiles after 0, 4, and 12 months of GH treatment in children with an idiopathic GH deficiency. We compared the effects of GH treatment on LDL-C by apoE phenotype. In total, 66 children with idiopathic GH deficiency and 89 healthy children were classified into subgroups according to apoE phenotype. The intervention included GH replacement therapy for 12 months. The relationship between apoE phenotype and reduced LDL-C induced by GH treatment was measured. Concentrations of LDL-C and apoB were highest in the apoE4/3 group (n = 13), second highest in the apoE3/3 group (n = 46), and lowest in the apoE3/2 group (n = 7), whereas apoE concentrations were highest in the apoE3/2 group and lowest in the apoE4/3 group. The apoE4/3 group had significantly reduced LDL-C and apoB concentrations at months 4 and 12, whereas the apoE3/3 and apoE3/2 groups showed no changes. LDL-C concentrations did not differ among the three groups after 12 months. The trend in apoE concentration did not change among the groups. Children with a GH deficiency carrying apoE4 had higher baseline LDL-C concentrations and experienced a greater reduction in LDL-C after GH replacement therapy than those without apoE4.