Genetic invalidation of Lp-PLA₂ as a therapeutic target: Large-scale study of five functional Lp-PLA₂-lowering alleles.

ABSTRACT: Aims Darapladib, a potent inhibitor of lipoprotein-associated phospholipase A₂ (Lp-PLA₂), has not reduced risk of cardiovascular disease outcomes in recent randomized trials. We aimed to test whether Lp-PLA₂ enzyme activity is causally relevant to coronary heart disease. Methods In 72,657 patients with coronary heart disease and 110,218 controls in 23 epidemiological studies, we genotyped five functional variants: four rare loss-of-function mutations (c.109+2T > C (rs142974898), Arg82His (rs144983904), Val279Phe (rs76863441), Gln287Ter (rs140020965)) and one common modest-impact variant (Val379Ala (rs1051931)) in PLA2G7, the gene encoding Lp-PLA₂. We supplemented de-novo genotyping with information on a further 45,823 coronary heart disease patie

SUBMITTER: Gregson JM 

PROVIDER: S-EPMC5460752 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature