The fine line between familial and polygenic hypercholesterolemia

Abstract

Evaluation of: Talmud PJ, Shah S, Whittall R et al. Use of low-density lipoprotein cholesterol gene score to distinguish patients with polygenic and monogenic hypercholesterolaemia: a case–control study. Lancet 381(9874), 1293–1301 (2013). Familial hypercholesterolemia (FH) is a common disorder caused by mutations in LDLR, APOB and PCSK9. However, many subjects with primary hypercholesterolemia did not demonstrate functional mutations in any of these genes. Genome-wide association studies have identified single nucleotide polymorphisms that influence the variability of LDL-C concentration. Talmud et al. have genotyped 12 common LDL cholesterol (LDL-C)-raising alleles in 640 patients with the clinical diagnosis of FH and in 3020 healthy subjects from the UK Whitehall II study. Approximately 50% of the FH patients did not possess a causative mutation and the mean weighted LDL-C gene score was significantly higher than in the controls, indicating a polygenic cause for their disorder. These results indicate t...