Hepatic HMG-CoA Reductase Activities in Patients with Heterozygous Familial Hypercholesterolemia

Abstract

Hepatic microsomal 3-hydroxy-3-methylglu-taryl coenzyme A (HMG-CoA) reductase (EC. 1. 1. 1. 34) activities were measured in 4 patients with heterozygous familial hepercholesterolemia (FH). Percutaneous needle liver biopsies were performed in 13 patients, who were classified into heterozygous FH group (n=4), heperlipidemic group (>200mg/dl in cholesterol, and/or >150mg/dl in triglyceride, n=4) and normolipidemic group (≤200mg/dl in cholesterol, ≤150mg/dl in triglyceride, n=5). The tissues were utilized for histological diagnoses and preparations of liver microsomes.
The mean±SE of HMG-CoA reductase activities was 71.8±33.9pmoles/min, mg microsomal protein in heterozygous FH, 25.2±4.0 in hyperlipidemic group and 19.0±5.9 in normolipidemic group. There were no statistically significancies among these three groups, but the activities in two patients with heterozygous FH showed very high levels (126.1 and 134.8). There was a significant correlation between HMG-CoA reductase activities and plasma cholesterol levels of low density lipoprotein (r=0.723, p<0.01). The activities did not significantly correlate with plasma albumin concentrations.
These results indicate that the regulation of hepatic cholesterol synthesis in vivo is impaired to various degress in heterozygous FH.