Study questions effectiveness of genetic testing strategy for inherited high cholesterol

A substantial proportion of individuals with a clinical diagnosis of Familial Hypercholesterolaemia (FH) inherit a combination of small-effect changes in several genes (polygenic) rather than a large-effect mutation in a single gene (monogenic), according to a new paper in The Lancet . The findings have implications for the majority of national guidelines on family screening for FH, that advocate testing relatives of all individuals with a clinical diagnosis of FH, including those of the UK National Institute for Health and Clinical Excellence (NICE). "Cascade [family] testing of the roughly 40 per cent of patients with a clinical diagnosis of FH and an identifiable causative mutation would eliminate staff and screening costs associated with screening relatives of the remaining 60 per cent of patients without an identifiable mutation. This is very likely to be more cost-effective, but proving this will require a more detailed analysis," says lead researcher Steve Humphries, UCL Centre for Cardiovascular Genetics. We propose that the clinical diagnosis of FH should be restricted to those in whom a mutation can be identified, whereas those with no detected mutation should be given the clinical diagnosis of polygenic hypercholesterolaemia. Steve Humphries, UCL Centre for Cardiovascular Genetics FH is one of the most common inherited disorders affecting over 12 million people worldwide (1 in 500 of the general population). It causes very high levels of low-density lipoprotein cholesterol (LDL-C) or "bad cholesterol" in the blood, and if untreated, results in a five to eight times greater risk of early coronary heart disease (CHD).