Apolipoprotein B Arg3500Gln Mutation Prevalence in Children With Hypercholesterolemia: A French Multicenter Study

Abstract

ABSTRACTBackgroundFamilial defective apolipoprotein B‐100, a dominantly inherited form of hypercholesterolemia caused by a single Arg3500Gln mutation, is silent in childhood but may confer a high risk of cardiovascular disease in adulthood. The objective was to determine the prevalence of familial defective apolipoprotein B‐100 in hypercholesterolemic French children and to provide a basis for targeting screening efforts in this population.MethodsOne hundred ninety children attending 13 pediatric clinics distributed throughout France were included based on the presence of type IIa hypercholesterolemia with a plasma low‐density lipoprotein–cholesterol level of more than 130 mg/dL. The Arg3500Gln mutation was detected in dried blood spots using a polymerase chain reaction assay combined with enzymatic restriction.ResultsThree hyperlipidemia phenotypes were found: monogenic dominant pure hypercholesterolemia (n = 117), polygenic hypercholesterolemia (n = 43), and combined hyperlipidemia (n = 11). Three unrelated children were heterozygous for the Arg3500Gln mutation; all three had monogenic dominant pure hypercholesterolemia (3/94 families; 3.2%), yielding a prevalence of 1.83% (3/164) in hypercholesterolemic children, which is similar to prevalences reported in European adults.ConclusionsThe familial defective apolipoprotein B‐100 mutation was common (1/31) in children with a phenotype of familial hypercholesterolemia, supporting screening in this population with the goal of preventing premature cardiovascular events.