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

Gregson, John M. ; Freitag, Daniel F. ; Surendran, Praveen ; Stitziel, Nathan O. ; Chowdhury, Rajiv ; Burgess, Stephen ; Kaptoge, Stephen ; Gao, Pei ; Staley, James R. ; Willeit, Peter ; Nielsen, Sune F. ; Caslake, Muriel ; Trompet, Stella ; Polfus, Linda M. ; Kuulasmaa, Kari ; Kontto, Jukka ; Perola, Markus ; Blankenberg, Stefan ; Veronesi, Giovanni ; Gianfagna, Francesco ; Männistö, Satu ; Kimura, Akinori ; Lin, Honghuang ; Reilly, Dermot F. ; Gorski, Mathias ; Mijatovic, Vladan ; Munroe, Patricia B. ; Ehret, Georg B. ; Thompson, Alex ; Uria-Nickelsen, Maria ; Malarstig, Anders ; Dehghan, Abbas ; Vogt, Thomas F. ; Sasaoka, Taishi ; Takeuchi, Fumihiko ; Kato, Norihiro ; Yamada, Yoshiji ; Kee, Frank ; Müller-Nurasyid, Martina ; Ferrières, Jean ; Arveiler, Dominique ; Amouyel, Philippe ; Salomaa, Veikko ; Boerwinkle, Eric ; Thompson, Simon G. ; Ford, Ian ; Wouter Jukema, J. ; Sattar, Naveed ; Packard, Chris J. ; Shafi Majumder, Abdulla al ; Alam, Dewan S. ; Deloukas, Panos ; Schunkert, Heribert ; Samani, Nilesh J. ; Kathiresan, Sekar ; Nordestgaard, Børge G. ; Saleheen, Danish ; Howson, Joanna M. M. ; Di Angelantonio, Emanuele ; Butterworth, Adam S. ; Danesh, John



Abstract

Aims: Darapladib, a potent inhibitor of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), has not reduced risk of cardiovascular disease outcomes in recent randomized trials. We aimed to test whether Lp-PLA(2) 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 ...

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