APCSK9Missense Variant Associated with a Reduced Risk of Early-Onset Myocardial Infarction

Abstract

Cohen et al. (March 23, 2006, issue)¹ describe a missense variant in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene that was associated with reductions in low-density lipoprotein (LDL) cholesterol levels and in the risk of coronary heart disease. They report that among whites, the L allele at R46L (rs11591147) was associated with a 15% reduction in plasma levels of LDL cholesterol and a decreased risk of incident coronary heart disease (hazard ratio, 0.50; 95% confidence interval [CI], 0.32 to 0.79; P=0.003). Although the association of R46L with reduced LDL cholesterol levels has been convincingly replicated,² it remains unclear whether R46L is associated with a reduced risk of clinical events.