Study shows mutations in NPC1L1 protein cut coronary heart disease

A new study part-funded by US pharma giant Merck & Co (NYSE: MRK) has found that mutations in a gene encoding the NPC1L1 protein are linked to reduced LDL cholesterol levels. The data could have ramifications for Merck’s cholesterol-lowering drug Zetia (ezetimibe).

The authors of the research, published in The New England Journal of Medicine, sequenced the exons of NPC1L1 in 7,364 patients with coronary heart disease and in 14,728 controls without such disease who were of European, African, or South Asian ancestry. The study aimed to show that protein-inactivating mutations in NPC1L1 reduce both the LDL cholesterol level and the risk of coronary heart disease.

They identified carriers of inactivating mutations (nonsense, splice-site, or frameshift mutations) and genotyped a specific inactivating mutation (p.Arg406X) in 22,590 patients with coronary heart disease and in 68,412 controls. The study tested the association between the presence of an inactivating mutation and both plasma lipid levels and the risk of coronary heart disease.