BACKGROUND: There is increasing evidence that lipoprotein-associated phospholipase A2 (LpPLA2) is associated with cardiovascular disease. However, it is still unclear whether LpPLA2 is simply a marker or has a causal role as either a pro- or anti-atherogenic factor. METHODS: We analyzed the association of five polymorphisms (-1357G>A, -403T>C, Arg92His, Ile198Thr, Ala379Val) and related haplotypes at the PLA2G7 locus with angiographic coronary artery disease (CAD), plasma LpPLA2 activity, and long-term survival in 3234 patients scheduled for coronary angiography. RESULTS: The promoter variant -403C and His(92) were associated with a decrease and Val(379) with an increase in plasma LpPLA2 activity. Both coding variants revealed a clear gene-dose effect. Interestingly, the rare Thr(198) allele, which was not associated with any change in plasma LpPLA2 activity, was more frequent in subjects without CAD (P = 0.009), with an adjusted odds ratio for CAD of 0.69 (95% CI: 0.49-0.96; P = 0.029). None of the analyzed variants showed any robust association with all-cause or cardiovascular mortality. CONCLUSION: Irrespective of the significant association between some variants with plasma LpPLA2 activity, it is still unclear whether these polymorphisms or haplotypes are associated with the risk and outcome of cardiovascular disease in Caucasians.
BACKGROUND: There is increasing evidence that lipoprotein-associated phospholipase A2 (LpPLA2) is associated with cardiovascular disease. However, it is still unclear whether LpPLA2 is simply a marker or has a causal role as either a pro- or anti-atherogenic factor. METHODS: We analyzed the association of five polymorphisms (-1357G>A, -403T>C, Arg92His, Ile198Thr, Ala379Val) and related haplotypes at the PLA2G7 locus with angiographic coronary artery disease (CAD), plasma LpPLA2 activity, and long-term survival in 3234 patients scheduled for coronary angiography. RESULTS: The promoter variant -403C and His(92) were associated with a decrease and Val(379) with an increase in plasma LpPLA2 activity. Both coding variants revealed a clear gene-dose effect. Interestingly, the rare Thr(198) allele, which was not associated with any change in plasma LpPLA2 activity, was more frequent in subjects without CAD (P = 0.009), with an adjusted odds ratio for CAD of 0.69 (95% CI: 0.49-0.96; P = 0.029). None of the analyzed variants showed any robust association with all-cause or cardiovascular mortality. CONCLUSION: Irrespective of the significant association between some variants with plasma LpPLA2 activity, it is still unclear whether these polymorphisms or haplotypes are associated with the risk and outcome of cardiovascular disease in Caucasians.
Authors: Harald Grallert; Josée Dupuis; Joshua C Bis; Abbas Dehghan; Maja Barbalic; Jens Baumert; Chen Lu; Nicholas L Smith; André G Uitterlinden; Robert Roberts; Natalie Khuseyinova; Renate B Schnabel; Kenneth M Rice; Fernando Rivadeneira; Ron C Hoogeveen; João Daniel Fontes; Christa Meisinger; John F Keaney; Rozenn Lemaitre; Yurii S Aulchenko; Ramachandran S Vasan; Stephen Ellis; Stanley L Hazen; Cornelia M van Duijn; Jeanenne J Nelson; Winfried März; Heribert Schunkert; Ruth M McPherson; Heide A Stirnadel-Farrant; Bruce M Psaty; Christian Gieger; David Siscovick; Albert Hofman; Thomas Illig; Mary Cushman; Jennifer F Yamamoto; Jerome I Rotter; Martin G Larson; Alexandre F R Stewart; Eric Boerwinkle; Jacqueline C M Witteman; Russell P Tracy; Wolfgang Koenig; Emelia J Benjamin; Christie M Ballantyne Journal: Eur Heart J Date: 2011-10-14 Impact factor: 29.983
Authors: Alexander Thompson; Pei Gao; Lia Orfei; Sarah Watson; Emanuele Di Angelantonio; Stephen Kaptoge; Christie Ballantyne; Christopher P Cannon; Michael Criqui; Mary Cushman; Albert Hofman; Chris Packard; Simon G Thompson; Rory Collins; John Danesh Journal: Lancet Date: 2010-05-01 Impact factor: 79.321
Authors: Juan P Casas; Ewa Ninio; Andrie Panayiotou; Jutta Palmen; Jackie A Cooper; Sally L Ricketts; Reecha Sofat; Andrew N Nicolaides; James P Corsetti; F Gerry R Fowkes; Ioanna Tzoulaki; Meena Kumari; Eric J Brunner; Mika Kivimaki; Michael G Marmot; Michael M Hoffmann; Karl Winkler; Winfred März; Shu Ye; Heide A Stirnadel; S Matthijs Boekholdt; Kay-Tee Khaw; Steve E Humphries; Manjinder S Sandhu; Aroon D Hingorani; Philippa J Talmud Journal: Circulation Date: 2010-05-17 Impact factor: 29.690
Authors: Keane K Lee; Stephen P Fortmann; Ann Varady; Joan M Fair; Alan S Go; Thomas Quertermous; Mark A Hlatky; Carlos Iribarren Journal: BMC Cardiovasc Disord Date: 2011-06-29 Impact factor: 2.298