Association of specific LDL receptor gene mutations with differential plasma lipoprotein response to simvastatin in young French Canadians with heterozygous familial hypercholesterolemia.
In familial hypercholesterolemia (FH), the efficacy of the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase shows considerable interindividual variation, and several genetic and environmental factors can contribute to explaining this variability. A randomized, double-blind, placebo-controlled clinical trial with simvastatin, an HMG-CoA reductase inhibitor, was conducted in 63 children and adolescents with heterozygous FH. The patients were grouped according to known LDL receptor genotype. After 6 weeks of treatment with 20 mg/d simvastatin, the mean reduction in plasma LDL cholesterol in patients with the W66G mutation (n=14) was 31%, whereas in the deletion>15 kb (n=23) and the C646Y mutation groups (n=10), it was 38% and 42%, respectively (P