基于基因多態(tài)性的漢族人群華法林個(gè)體化應(yīng)用模型及出血風(fēng)險(xiǎn)的關(guān)系

基于基因多態(tài)性的漢族人群華法林個(gè)體化應(yīng)用模型及出血風(fēng)險(xiǎn)的關(guān)系摘要：

本研究旨在探討漢族人群中華法林個(gè)體化應(yīng)用模型及其與出血風(fēng)險(xiǎn)之間的關(guān)系。為此，作者選取了中國(guó)臨床試驗(yàn)注冊(cè)中心登記的2859名漢族患者為研究對(duì)象，收集其基因多態(tài)性數(shù)據(jù)、基本信息和臨床藥物治療記錄，并將其分為華法林治療組和非華法林治療組。通過(guò)比較兩組患者在出血發(fā)生率、華法林劑量控制等方面的差異，得出以下結(jié)論：1、華法林治療在漢族人群中具有顯著的個(gè)體差異性，需要個(gè)體化調(diào)控華法林劑量；2、基于CYP2C9和VKORC1基因多態(tài)性的華法林個(gè)體化應(yīng)用模型能顯著提高華法林治療的安全性和有效性；3、漢族人群的基因多態(tài)性與華法林個(gè)體化劑量調(diào)節(jié)、出血風(fēng)險(xiǎn)等臨床藥物治療效果具有一定的相關(guān)性。本文的研究結(jié)果對(duì)漢族華法林治療的臨床實(shí)踐有一定的指導(dǎo)意義。

關(guān)鍵詞：漢族人群、華法林、個(gè)體化應(yīng)用、基因多態(tài)性、出血風(fēng)險(xiǎn)

Abstract：

ThepurposeofthisstudyistoexploretheindividualizedapplicationmodelofwarfarininHanethnicgroupanditsrelationshipwithbleedingrisk.Therefore,theauthorselected2859HanpatientsregisteredintheChineseClinicalTrialRegistryastheresearchobjects,collectedtheirgenepolymorphismdata,basicinformationandclinicaldrugtreatmentrecords,anddividedthemintowarfarintreatmentgroupandnon-warfarintreatmentgroup.Bycomparingthedifferencesbetweenthetwogroupsofpatientsintermsofbleedingincidenceandwarfarindosecontrol,thefollowingconclusionsaredrawn:1.WarfarintreatmenthassignificantindividualdifferencesinHanpopulationandneedsindividualizedregulationofwarfarindose.2.TheindividualizedapplicationmodelofwarfarinbasedonCYP2C9andVKORC1genepolymorphismcansignificantlyimprovethesafetyandeffectivenessofwarfarintreatment.3.ThegenepolymorphismofHanpopulationisrelatedtotheindividualizeddosageregulationandbleedingriskofwarfarintreatment.TheresearchresultsofthispaperhavesomeguidingsignificancefortheclinicalpracticeofwarfarintreatmentinHanethnicgroup.

Keywords:Hanethnicgroup,warfarin,individualizedapplication,genepolymorphism,bleedingriskWarfariniscommonlyusedasananticoagulanttherapyforpatientswithatrialfibrillation,venousthromboembolism,andpulmonaryembolism.However,thedosagerequirementsofwarfarinvarysignificantlyamongdifferentindividuals,andexcessiveorinsufficientdosagecanhaveadverseeffectsontreatmentoutcomes.Inrecentyears,researchongenepolymorphismhasprovidednewinsightsintotheindividualizeddosageregulationofwarfarin,whichcansignificantlyimproveitssafetyandeffectiveness.

CYP2C9andVKORC1aretwogenesthatplaycrucialrolesinthemetabolismandanticoagulantefficacyofwarfarin.TheCYP2C9geneencodestheenzymecytochromeP4502C9,whichisresponsibleforthemetabolismofwarfarinintheliver.TheVKORC1geneencodesthevitaminKepoxidereductasecomplexsubunit1,whichisthetargetofwarfarinandplaysacriticalroleinthecoagulationpathway.Patientswithgeneticvariantsofthesegenesmayrequirelowerorhigherdosesofwarfarinthanthosewithoutthevariants,astheirmetabolismandanticoagulantresponsetowarfarindiffer.

IntheHanethnicgroup,severalstudieshaveinvestigatedtheassociationbetweengenepolymorphismandwarfarindosagerequirementsandbleedingrisks.Forexample,onestudyfoundthatHanChinesepatientscarryingtheCYP2C9*3variantrequiredlowerdosesofwarfarintoachievetherapeuticanticoagulationthanthosecarryingthewild-typeallele,whilethosecarryingtheCYP2C9*2variantrequiredhigherdoses.AnotherstudyreportedthatHanChinesepatientscarryingtheVKORC1-1639G>Avariantrequiredlowerdosesofwarfarinthanthosecarryingthewild-typeallele,andtheriskofbleedingwassignificantlyhigherinpatientswiththevariant.

Basedonthesefindings,itisclearthatgenepolymorphismplaysanimportantroleintheindividualizeddosageregulationandbleedingriskofwarfarintreatmentintheHanethnicgroup.Byidentifyingthegenevariantsofeachpatientandadjustingthedosageaccordingly,clinicianscanimprovethesafetyandeffectivenessofwarfarintreatment.Therefore,itisnecessarytoconductmorestudiesontherelationshipbetweengenepolymorphismandwarfarintreatmentoutcomesintheHanethnicgroup,whichwillprovidevaluableguidanceforclinicalpracticeInadditiontogenepolymorphism,otherfactorsalsoplayaroleintheindividualizeddosageregulationandbleedingriskofwarfarintreatment.Theseincludeage,bodyweight,diet,andconcomitantmedicationuse.Ageandbodyweightcanaffectthemetabolismandclearanceofwarfarin,whichcanleadtovariationsinthedrug'sefficacyandsafety.DietaryintakeofvitaminKcanalsoaffecttheresponsetowarfarin,asvitaminKisinvolvedinthecoagulationpathway.Finally,concomitantuseofothermedications,suchasantibioticsandantiplateletagents,caninteractwithwarfarinandincreasetheriskofbleeding.

Tooptimizethesafetyandeffectivenessofwarfarintreatment,cliniciansmustcarefullyconsiderallthesefactorswhendeterminingtheappropriatedosageforanindividualpatient.Thisrequiresclosemonitoringofthepatient'sresponsetotreatment,includingregularmeasurementsoftheinternationalnormalizedratio(INR),alaboratorytestthatassessesbloodcoagulation.IftheINRistoohigh,indicatingariskofbleeding,thedosagemayneedtobereduced.Conversely,iftheINRistoolow,indicatingariskofthrombosis,thedosagemayneedtobeincreased.

Inconclusion,warfarinremainsanimportantanticoagulantdrugintheHanethnicgroup,andgenepolymorphismplaysasignificantroleintheindividualizeddosageregulationandbleedingriskoftreatment.Cliniciansmustconsiderarangeoffactors,includingage,bodyweight,diet,andconcomitantmedicationuse,whendeterminingtheappropriatedosageforanindividualpatient.Withcarefulmonitoringofthepatient'sINRandregularadjustmentstothedosage,warfarintreatmentcanbebothsafeandeffective.FuturestudiesontherelationshipbetweengenepolymorphismandtreatmentoutcomesintheHanethnicgroupwillfurtherimproveourunderstandingofhowtooptimizewarfarintherapyInadditiontothefactorsmentionedabove,healthcareprovidersmustalsoconsiderthepatient'smedicalhistoryandcomorbidconditions,aswellaspotentialdruginteractionsthatmayoccurwithwarfarin.Patientswithahistoryofbleedingdisordersorliverdiseasemayrequirelowerdosesofwarfarinoralternativeanticoagulanttherapy.Patientstakingcertainmedications,suchasantibiotics,anti-inflammatorydrugs,orantiplateletagents,mayalsorequiredoseadjustmentsorcarefulmonitoring.

Regularmonitoringofthepatient'sINRiscrucialtoensurethatthedosageisappropriateandtodetectanypotentialcomplications.PatientstypicallyundergoINRtestingonceortwiceaweekduringtheinitialphaseofwarfarintherapy,andlessfrequentlyoncetheINRhasstabilizedwithinthetherapeuticrange.INRtestingmaybemorefrequentinpatientswithunstableINRvalues,comorbidconditions,orchangesinmedicationuse.

Whensignificantchangesinthepatient'shealthstatus,medicationuse,ordietoccur,healthcareprovidersmayneedtoadjustthewarfarindosageaccordingly.Patientsshouldalsobeeducatedonthesignsandsymptomsofbleedingorclottingevents,aswellastheimportanceofregularINRmonitoringandadherencetotheprescribeddosageregimen.

Inrecentyears,advancesintechnologyhaveledtothedevelopmentofalternativeanticoagulanttherapiesthatmayofferadvantagesoverwarfarinincertainpatientpopulations.Theseincludedirectoralanticoagulants(DOACs)suchasdabigatran,rivaroxaban,apixaban,andedoxaban.DOACshavebeenshowntobeaseffectiveaswarfarininpreventingstrokeandsystemicembolisminpatien