ApoE4 determines the reduction in LDL-C after GH replacement therapy in children with an idiopathic GH deficiency

Abstract

Context: 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. Objectives: We examined whether GH-deficient children carrying apoE4 exhibited a greater reduction in LDL-C after GH replacement therapy. Design and Setting:Wedetermined 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. Subjects: In total, 66 children with idiopathic GH deficiency and 89 healthy children were classified into subgroups according to apoE phenotype. Intervention: The intervention included GH replacement therapy for 12 months. Main Outcome Measures: The relationship between apoE phenotype and reduced LDL-C induced by GH treatment was measured. Results: 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. Conclusions: 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.