Thiopurine S-methyltransferase polymorphisms and thiopurine toxicity in treatment of inflammatory bowel disease

(整期优先)网络出版时间:2010-12-22
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AIM:Toevaluatetherelationshipbetweenthiopu-rineS-methyltransferase(TPMT)polymorphismsandthiopurine-inducedadversedrugreactions(ADRs)ininflammatoryboweldisease(IBD).METHODS:EligiblearticlesthatcomparedthefrequencyofTPMTpolymorphismsamongthiopurine-tolerantand-intolerantadultIBDpatientswereincluded.StatisticalanalysiswasperformedwithReviewManager5.0.Sub-analysis/sensitivityanalysiswasalsoperformed.RESULTS:Ninestudiesthatinvestigatedatotalof1309participantsmetourinclusioncriteria.Theinci-denceofTPMTgenemutationwasincreased2.93-fold(95%CI:1.68-5.09,P=0.0001)and5.93-fold(95%CI:2.96-11.88,P<0.00001),respectively,inIBDpatientswiththiopurine-inducedoverallADRsandbonemarrowtoxicity(BMT),comparedwithcontrols.TheORforTPMTgenemutationinIBDpatientswiththiopurine-inducedhepatotoxicityandpancreatitiswas1.51(95%CI:0.54-4.19,P=0.43)and1.02(95%CI:0.26-3.99,P=0.98)vscontrols,respectively.CONCLUSION:Thismeta-analysissuggeststhattheTPMTpolymorphismsareassociatedwiththiopurine-inducedoverallADRsandBMT,butnotwithhepatotoxicityandpancreatitis.