FCHL (familial combined hyperlipidaemia) is characterized by multiple phenotypes that are shaped by genes, the environment and time. A longitudinal study by Brouwers and co-workers, which appears in this issue of Clinical Science, points to the central role of the liver in defining the FCHL phenotypes and demonstrates how they vary over time in relation to energy excess. On the basis of their work and that of others, we propose that FCHL is a multiple gene/multiple pathway/multiple phenotype disease. The key feature of this model of common complex disease is that it posits testable faults in definable metabolic pathways, which supply the genetic underpinning of the disorder.
© The Authors Journal compilation © 2007 Biochemical Society