biostudies-literatureHolmes MVEconomic and Social Research CouncilBritish Heart FoundationNHLBI NIH HHSMedical Research CouncilNational Institute for Health Research (NIHR)144-50https://www.ebi.ac.uk/biostudies/studies/S-EPMC4212409biostudies-literatureUnknown7(2)<h4>Background</h4>Secretory phospholipase A2 (sPLA2) enzymes are considered to play a role in atherosclerosis. sPLA2 activity encompasses several sPLA2 isoenzymes, including sPLA2-V. Although observational studies show a strong association between elevated sPLA2 activity and CHD, no assay to measure sPLA2-V levels exists, and the only evidence linking the sPLA2-V isoform to atherosclerosis progression comes from animal studies. In the absence of an assay that directly quantifies sPLA2-V levels, we used PLA2G5 mRNA levels in a novel, modified Mendelian randomization approach to investigate the hypothesized causal role of sPLA2-V in coronary heart disease (CHD) pathogenesis.<h4>Methods and results</h4>Using data from the Advanced Study of Aortic Pathology, we identified the single-nucleotidCirculation. Cardiovascular geneticsNovel genetic approach to investigate the role of plasma secretory phospholipase A2 (sPLA2)-V isoenzyme in coronary heart disease: modified Mendelian randomization analysis using PLA2G5 expression levels.PMC4212409RG/08/008/25291G1000143P01 HL-49058ES/K005146/1R01 HL-105924NF-SI-0512-10114P01 HL-62426R01 HL-91056G0802432RG/10/12/28456MR/K013351/1R01 HL-81680ES/J023299/1P01 HL-077101R01 HL036310R01 HL-64035MR/K006584/1G0401527T32 HL-07692ES/H029745/1FS/13/6/29977RG/10/001/27643Matthai WPsaty BMFranco-Cereceda ASiscovick DSRice KStark KScharnagl HMelander OWilensky RGo AAsselbergs FWGudnason VBruse PHoffmann MMSchreiber SHengstenberg CLaaksonen RLieb WUitterlinden AStewart AFGabriel SBKeating BJMunzel TDehghan ARisch NSchwartz SMKathiresan SAherrahrou ZDevaney JMorrison AKnowles JTomaschitz ANelson CPLindsay JMKlopp NHall ASSidney SKonig IRTiret LLevy DGretarsdottir SCupples LFischer MProust CPreuss MHolm HThorsteinsdottir UVoight BFZeller TBoekholdt SMAltshuler DWaksman RErdmann JBlankenberg SSalomaa VMarciante KBohm BOJarinova OZiegler AKhaw KTSmith AJTang HSchillert ADeloukas PWhitteman JKong APichard ADQu LWells GAHofman AExeter HJMcPherson RHall ACARDIoGRAM ConsortiumGrammer TBDobnig HIribarren CRamachandran VHlatky MTaylor KDWagner AKReiner APLoley CDonnell CJBalmforth AJWinkler KSchnabel RNicaud VGrosshennig ACooper JAPeltonen LKleber MPeters AMallat ZRotter JIDandona SBraund PSThorleifsson GRoberts RWright BJReilly MPStefansson KMusunuru KAndersen KMedack ABoerwinkle EVan't Hooft FHofker MLi KWGulcher JRDemissie-Banjaw SAbsher DNahrstedt JPerret CFolsom AWillenborg CGlazer NSchunkert HTalmud PJMeitinger TMeinitzer ARenner WPilz SSinning CChen LOnland-Moret NCMeisinger CLi MSatler LWalker MCCambien FSamani NJMyers RHolmes MVVolcik KMooser VThorgeirsson GAssimes TLGuiducci CEriksson PBoer JMRader DJMarz WQuertermous TDoering ALumley TBis JKivimaki MLinsel-Nitschke PHeckbert SIllig TGuardiola MRupprecht HJvan Duijn CKent KMSofat RFortmann SWaterworth DMChen IYEpstein SEKnouff CWWinkelmann BRThompson JRHarris TBickel CSmith ALackner KBurnett MSFolkersen LHingorani ADWichmann H-Barbalic MElosua RBall SGSmith NBurtt NHalperin EHakonarson HHWild PStojakovic THumphries SEKumari MfalseNovel genetic approach to investigate the role of plasma secretory phospholipase A2 (sPLA2)-V isoenzyme in coronary heart disease: modified Mendelian randomization analysis using PLA2G5 expression levels.<h4>Background</h4>Secretory phospholipase A2 (sPLA2) enzymes are considered to play a role in atherosclerosis. sPLA2 activity encompasses several sPLA2 isoenzymes, including sPLA2-V. Although observational studies show a strong association between elevated sPLA2 activity and CHD, no assay to measure sPLA2-V levels exists, and the only evidence linking the sPLA2-V isoform to atherosclerosis progression comes from animal studies. In the absence of an assay that directly quantifies sPLA2-V levels, we used PLA2G5 mRNA levels in a novel, modified Mendelian randomization approach to investigate the hypothesized causal role of sPLA2-V in coronary heart disease (CHD) pathogenesis.<h4>Methods and results</h4>Using data from the Advanced Study of Aortic Pathology, we identified the single-nucleotid2014-01-01T00:00:00Z2014 Apr2026-05-03T22:35:06.359Z2025-07-02T03:05:37.502ZS-EPMC42124092456341810.1161/CIRCGENETICS.113.00027110.1161/circgenetics.113.000271