Association of alcohol dehydrogenase and aldehyde dehydrogenase 2 genetic polymorphisms with serum lipid profile: meta-analysis of mendelian randomisation studies

(整期优先)网络出版时间:2014-04-14
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BackgroundAlcoholdehydrogenase(ADH)andaldehydedehydrogenase2(ALDH2)arethekeyenzymesforalcoholmetabolism.SeveralgeneticstudieshaveinvestigatedtheassociationbetweenADHandALDH2geneticpolymorphismsandserumlipidprofile(SLP),however,theresultswereinconsistent.MethodsFourteenarticlesinvolving27,917participantswereincludedinthismeta-analysis.Weightedmeandifference(WMD)and95%confidenceintervals(CIs)werepresentedusingrandomeffectsmodel.PublicationbiaswasevaluatedbyfunnelplotandBegg’stest.Inaddition,tofurtherexploretheheterogeneity,subgroupanalysiswereperformed.ResultsOverall,therewasnoassociationbetweenADHgeneticpolymorphismsandSLPwithnoregardfordrinkingstatus.However,comparedwithALDH2wildhomozygousgenotype,ALDH2mutantgenotypeswereassociatedwithsignificantdecreaseinserumhighdensitylipoproteincholesterol(HDLC)(WMD-1.80mg/dL,95%CI-1.88to-1.72,P<0.001)andtotalcholesterol(TC)levels(WMD-1.10mg/dL,95%CI-1.59to-0.62,P<0.001),andsignificantincreaseinserumlowdensitylipoproteincholesterol(LDL-C)level(WMD0.30mg/dL,95%CI0.18to0.43,P<0.001).Althoughtherewasnosignificantdifferenceinserumtriglyceridelevelintheoverallpopulation,subgroupanalysisrevealedthatcomparedwithALDH2*1wildhomozygote,ALDH2*2alleledisplayedasignificantdifferenceinserumtriglyceridelevelbetweenthefemaleandmale(female:WMD1.69mg/dl,95%CI1.08to2.30,P<0.001;male:WMD-6.42mg/dL,95%CI-12.15to-0.68,P=0.028).ConclusionADHgeneticpolymorphismhasnoassociationwithSLP,regardlessofsexcategoryanddrinkingstatus.ALDH2geneticpolymorphismhasslightassociationwithHDL-C,LDL-CandTClevelsandsex-specificassociationwithserumtriglyceridelevel.WhetherornottheassociationbetweenADH2geneticpolymorphismsandSLPisresultedfromalcoholconsumptionneedsfurtherinvestigation.