Effects of paraoxonase activity and gene polymorphism on coronary vasomotion.docVIP

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Effects of paraoxonase activity and gene polymorphism on coronary vasomotion.doc

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Effects of paraoxonase activity and gene polymorphism on coronary vasomotion

Dunetetal.EJNMMIResearch2011,1:27 /content/1/1/27 ORIGINAL RESEARCH OpenAccess Effectsofparaoxonaseactivityandgene polymorphismoncoronaryvasomotion VincentDunet1,JuanRuiz2,GillesAllenbach1,PaolaIzzo2,RichardWJames3andJohnOPrior1* Abstract Background:Paraoxonase1[PON1]isrecognizedasaprotectiveenzymeagainstLDLoxidation,andPON1 polymorphismhasbeendescribedasafactorinfluencingcoronaryheartdisease[CHD]freesurvival.Ascoronary vasoreactivityisasurrogateoffuturecardiovascularevents,weaimedatassessingtherespectiveeffectofthe PON1genotypeandactivityoncoronaryvasoreactivityinapopulationoftype2diabeticpatients. Methods:Nineteenpatientswithtype2diabetesmellitusunderwent 82RbcardiacPET/CTtoquantifymyocardial bloodflow[MBF]atrest,duringcoldpressortesting[CPT],andduringadenosine-inducedhyperaemiatocompute myocardialflowreserve[MFR].TheywereallocatedaccordingtoQ192RandL55Mpolymorphismsintothree groups(wild-typeandLM/QRheterozygotes,MMhomozygotes,andRRhomozygotes)andunderwenta measurementofplasmaticPON1activity.Relationsbetweenrest-MBF,stress-MBF,MFR,andMBFresponsetoCPT andPON1genotypesandPON1activitywereassessedusingSpearman’scorrelationandmultivariatelinear regressionanalysis. Results:AlthoughPON1activitywassignificantlyassociatedwithPON1polymorphism(p0.0001),therewasno significantrelationbetweenthePON1genotypesandtherest-MBF,stress-MBF,orMBFresponsetoCPT(p≥0.33). ThePON1activitysignificantlycorrelatedwiththeHDLplasmalevel(r=0.63,p=0.005),age(r=-0.52,p= 0.027),andMFR(r=0.48,p=0.044).Moreover,onmultivariateanalysis,PON1activitywasindependently associatedwithMFR(p=0.037). Conclusion:OurstudysupportsanindependentassociationbetweenPON1activityandMFR.WhetherPON1 contributestopromotecoronaryvasoreactivitythroughitsantioxidantactivityremainstobeelucidated.This putativemechanismcouldbethebasisoftheincreasedriskofCHDinpatientswithlowPON1activity. Keywords:paraoxonase,myocardialflowreserve,diabetes,rubidium-82 Background oxidativestressandplaqueformation.Theseantioxidant Coronaryhea