Homozygous familial hypercholesterolemia. A possible biochemical explanation of clinical heterogeneity.
Patients with homozygous familial hypercholesterolemia fall into two groups: one responds to diet and drug therapy; the other does not. Fibroblasts from patients in each group were compared for low-density lipoprotein suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and low-density lipoprotein binding. In fibroblasts from four therapy-responsive patients, low-density lipoprotein (100 mug per milliliter) suppressed 3-hydroxy-3-methylglutaryl coenzyme A reductase activity to 41 +/- 12 per cent of control (without low-density lipoprotein) whereas fibroblast enzyme activity from two therapy-unresponsive patients was not suppressed (P less than 0.001). Low-density lipoprotein binding to fibroblasts from both groups was defective as compared to normal controls. Fibroblasts from two therapy-responsive patients had specific binding of low-density lipoprotein of 27 +/- 4 per cent of normal -- greater than the 12 +/- 2 per cent (P less than 0.005) binding to fibroblasts from one therapy-unresponsive patient. These biochemical differences may help explain the variable response to therapy in homozygous familial hypercholesterolemia.
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006720:Homozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D066298:In Vitro Techniques; D007223:Infant; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D011485:Protein Binding
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL