Range of LDL cholesterol concentrations in severe hypercholesterolemia according to monogenic defects
LDL cholesterol concentrations might overlap in individuals with different genetic defects.[1,2] They might also vary according to the presence or absence of small-effect gene variants.[3,4] Homozygotes have the same mutation in two alleles of the same gene. Double heterozygotes have different mutations, one on each allele of the same gene. Compound heterozygotes have mutations in two different genes. LDLR null mutations defined as LDL receptor activity <2% in fibroblasts. LDLR defective mutations defined as LDL receptor activity 2 to 25% in fibroblasts.
References:
- Gidding SS, Champagne MA, de Ferranti SD, et al. The agenda for familial hypercholesterolemia: a scientific statement from the American Heart Association. Circulation 2015; 132:2167.
- Cuchel M, Bruckert E, Ginsberg HN, et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management—a position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J 2014; 35:2146.
- Talmud PJ, Shah S, Whittall R, et al. Use of low-density lipoprotein cholesterol gene score to distinguish patients with polygenic and monogenic familial hypercholesterolaemia: a case-control study. Lancet 2013; 381:1293.
- Futema M, Shah S, Cooper JA, et al. Refinement of variant selection for the LDL cholesterol genetic risk score in the diagnosis of the polygenic form of clinical familial hypercholesterolemia and replication in samples from 6 countries. Clin Chem 2015; 61:231.
Reproduced from: Santos RD, Gidding SS, Hegele RA, et al. Defining severe familial hypercholesterolaemia and the implications for clinical management: a consensus statement from the International Atherosclerosis Society Severe Familial Hypercholesterolemia Panel. Lancet Diabetes Endocrinol 2016; 4:850. Illustration used with the permission of Elsevier Inc. All rights reserved.
