Corsetti JP

References (2)

Title : PLA2G7 genotype, lipoprotein-associated phospholipase A2 activity, and coronary heart disease risk in 10 494 cases and 15 624 controls of European Ancestry - Casas_2010_Circulation_121_2284
Author(s) : Casas JP , Ninio E , Panayiotou A , Palmen J , Cooper JA , Ricketts SL , Sofat R , Nicolaides AN , Corsetti JP , Fowkes FG , Tzoulaki I , Kumari M , Brunner EJ , Kivimaki M , Marmot MG , Hoffmann MM , Winkler K , Marz W , Ye S , Stirnadel HA , Boekholdt SM , Khaw KT , Humphries SE , Sandhu MS , Hingorani AD , Talmud PJ
Ref : Circulation , 121 :2284 , 2010
Abstract : BACKGROUND: Higher lipoprotein-associated phospholipase A(2)(Lp-PLA2) activity is associated with increased risk of coronary heart disease (CHD), making Lp-PLA2 a potential therapeutic target. PLA2G7 variants associated with Lp-PLA2 activity could evaluate whether this relationship is causal. METHODS AND RESULTS: A meta-analysis including a total of 12 studies (5 prospective, 4 case-control, 1 case-only, and 2 cross-sectional studies; n=26 118) was undertaken to examine the association of the following: (1) Lp-PLA2 activity versus cardiovascular biomarkers and risk factors and CHD events (2 prospective studies; n=4884); (2) PLA2G7 single-nucleotide polymorphisms and Lp-PLA2 activity (3 prospective, 2 case-control, 2 cross-sectional studies; up to n=6094); and (3) PLA2G7 single-nucleotide polymorphisms and angiographic coronary artery disease (2 case-control, 1 case-only study; n=4971 cases) and CHD events (5 prospective, 2 case-control studies; n=5523). Lp-PLA2 activity correlated with several CHD risk markers. Hazard ratios for CHD events for the top versus bottom quartile of Lp-PLA2 activity were 1.61 (95% confidence interval, 1.31 to 1.99) and 1.17 (95% confidence interval, 0.91 to 1.51) after adjustment for baseline traits. Of 7 single-nucleotide polymorphisms, rs1051931 (A379V) showed the strongest association with Lp-PLA2 activity, with VV subjects having 7.2% higher activity than AAs. Genotype was not associated with risk markers, angiographic coronary disease (odds ratio, 1.03; 95% confidence interval, 0.80 to 1.32), or CHD events (odds ratio, 0.98; 95% confidence interval, 0.82 to 1.17). CONCLUSIONS: Unlike Lp-PLA2 activity, PLA2G7 variants associated with modest effects on Lp-PLA2 activity were not associated with cardiovascular risk markers, coronary atheroma, or CHD. Larger association studies, identification of single-nucleotide polymorphisms with larger effects, or randomized trials of specific Lp-PLA2 inhibitors are needed to confirm or refute a contributory role for Lp-PLA2 in CHD.
ESTHER : Casas_2010_Circulation_121_2284
PubMedSearch : Casas_2010_Circulation_121_2284
PubMedID: 20479152
Gene_locus related to this paper: human-PLA2G7

Title : Collaborative meta-analysis of individual participant data from observational studies of Lp-PLA2 and cardiovascular diseases - Ballantyne_2007_Eur.J.Cardiovasc.Prev.Rehabil_14_3
Author(s) : Ballantyne C , Cushman M , Psaty B , Furberg C , Khaw KT , Sandhu M , Oldgren J , Rossi GP , Maiolino G , Cesari M , Lenzini L , James SK , Rimm E , Collins R , Anderson J , Koenig W , Brenner H , Rothenbacher D , Berglund G , Persson M , Berger P , Brilakis E , McConnell JP , Sacco R , Elkind M , Talmud P , Cannon CP , Packard C , Barrett-Connor E , Hofman A , Kardys I , Witteman JC , Criqui M , Corsetti JP , Rainwater DL , Moss AJ , Robins S , Bloomfield H , Collins D , Wassertheil-Smoller S , Ridker P , Danesh J , Gu D , Nelson JJ , Thompson S , Zalewski A , Zariffa N , Di Angelantonio E , Kaptoge S , Thompson A , Walker M , Watson S , Wood A
Ref : Eur J Cardiovasc Prev Rehabil , 14 :3 , 2007
Abstract : BACKGROUND: A large number of observational epidemiological studies have reported generally positive associations between circulating mass and activity levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular diseases. Few studies have been large enough to provide reliable estimates in different circumstances, such as in different subgroups (e.g., by age group, sex, or smoking status) or at different Lp-PLA2 levels. Moreover, most published studies have related disease risk only to baseline values of Lp-PLA2 markers (which can lead to substantial underestimation of any risk relationships because of within-person variability over time) and have used different approaches to adjustment for possible confounding factors. OBJECTIVES: By combination of data from individual participants from all relevant observational studies in a systematic 'meta-analysis', with correction for regression dilution (using available data on serial measurements of Lp-PLA2), the Lp-PLA2 Studies Collaboration will aim to characterize more precisely than has previously been possible the strength and shape of the age and sex-specific associations of plasma Lp-PLA2 with coronary heart disease (and, where data are sufficient, with other vascular diseases, such as ischaemic stroke). It will also help to determine to what extent such associations are independent of possible confounding factors and to explore potential sources of heterogeneity among studies, such as those related to assay methods and study design. It is anticipated that the present collaboration will serve as a framework to investigate related questions on Lp-PLA2 and cardiovascular outcomes. METHODS: A central database is being established containing data on circulating Lp-PLA2 values, sex and other potential confounding factors, age at baseline Lp-PLA2 measurement, age at event or at last follow-up, major vascular morbidity and cause-specific mortality. Information about any repeat measurements of Lp-PLA2 and potential confounding factors has been sought to allow adjustment for possible confounding and correction for regression dilution. The analyses will involve age-specific regression models. Synthesis of the available observational studies of Lp-PLA2 will yield information on a total of about 15 000 cardiovascular disease endpoints.
ESTHER : Ballantyne_2007_Eur.J.Cardiovasc.Prev.Rehabil_14_3
PubMedSearch : Ballantyne_2007_Eur.J.Cardiovasc.Prev.Rehabil_14_3
PubMedID: 17301621
Gene_locus related to this paper: human-PLA2G7