47 KB124 KB30 KB199220252004Stocco, Gabrieleštevilka:2letnik:389 stranistr. 101-109ISSN:1318-2099COBISSID:18166489URN:URN:NBN:SI:doc-5FFC4HAUenAssociation of Radiology and OncologyRadiology and oncology (Ljubljana)6-Mercaptopurine6-merkaptopurinAzathioprineAzatioprinChromatography, High Pressure Liquidčrevesne boleznidiagnostikaDrug TherapyGeneticsGenotipGenotypeInflammatory Bowel DiseasesKromatografija visokotlačna, tekočinskaMethyltransferasesMetiltransferazemutacijePolimerazna, verižna reakcijaPolimorfizem, omejene dolžine fragmentovPolymerase Chain ReactionPolymorphism, Restriction Fragment LengththerapyVnetne, črevesne boleznizdravljenjePharmacogenetics of thiopurines| can posology be guided by laboratory data?|Background. The purpose of this study was to investigate the relationships between the presence of mutations in the TPMT gene, the consequent reduced enzymatic activity, and the clinical toxicity of the treatment with thiopurineantimetabolite drugs. Materials and methods. The study was performedon 44 patients with inflammatory bowel disease treated with AZA. DNA was extracted from blood samples collected from each patient, and genotyping was performed using specific polymerase chain reaction assays in order to detect the three more frequent mutations of the gene. Enzymatic activity was measured on red blood cell lysates by HPLC. Results. Among the subjects, 4 (9.0%) were heterozygous for mutations in the TPMT gene; no subject was homozygous for mutations in the TPMT gene. A complete concordance between TPMTmutated genotype and reduced enzymatic activity could be determined. The incidence of toxicity in the subjects with a mutated genotype was not different from that observed in the patients with a normal TPMT gene. Conclusion. Genotyping methods provide a simple and reliable DNA-based strategy to identify TPMT homozygotes that should avoid thiopurines administration. However, it seems that the most common, less dangerous forms of thiopurine toxicity could be caused by factors different from TPMT gene mutations examinedlzhodišče. Namen študije je bil ugotoviti odvisnost med mutacijami v genu TPMT, oslabljeno encimsko aktivnostjo zaradi teh mutacij in klinično toksičnostjo zdravljenja s tiopurinskimi antimetaboliti. Material in metode. Vštudijo smo vključili 44 bolnikov z vnetnim obolenjem črevesja, ki so bili zdravljeni z azatioprinom. Iz vzorcev krvi vsakega bolnika smo izločili DNK indoločili genotip s polimerazno verižno reakcijo, da bi tako našli tri najpogostejše genske mutacije. Encimsko aktivnost smo merili z visokoločljivostno tekočinsko kromatografijo na razgrajenih celičnih vsebinah rdečih krvničkah. Rezultati. Med izbranimi bolniki so bili 4 (9,0%) pri mutacijah gena TPMT heterozigotni, medtem ko med njimi pri teh mutacijah nihčeni bil homozigoten. Z raziskavo lahko potrdimo popolno soodvisnost med mutiranim genotipom TPMT in oslabljeno encimsko aktivnostjo. Pri primerjanju posameznikov z mutiranim genotipom in normalnim genotipom TPMT nismo opazili sprememb v toksičnosti. Zaključek. Z metodami genotipiziranja, ki temeljijo nastrateški uporabnosti DNK, je mogoče enostavno in zanesljivo odkriti homozigote TPMT - posameznike, ki jih ne smemo zdraviti s tiopurini. Hkrati paugotavljamo, da običajnejše in manj nevarne oblike toksičnosti tiopurinov povzročajo drugi dejavniki, ki niso povezani z mutacijami omenjenega gena TPMTTEXTznanstveno časopisjejournalsSlovenian National E-content AggregatorNational and University Library of SloveniaDruštvo radiologije in onkologije