Show simple item record

dc.creatorJekić, Biljana
dc.creatorLuković, Ljiljana
dc.creatorBunjevački, Vera
dc.creatorMilić, Vera
dc.creatorNovaković, Ivana
dc.creatorDamnjanović, Tatjana
dc.creatorMilašin, Jelena
dc.creatorPopović, Branka
dc.creatorMaksimović, Nela
dc.creatorDamjanov, Nemanja
dc.creatorRadunović, Goran
dc.creatorKovacević, Ljiljana
dc.creatorKrajinović, Maja
dc.date.accessioned2020-07-02T12:47:07Z
dc.date.available2020-07-02T12:47:07Z
dc.date.issued2013
dc.identifier.issn0031-6970
dc.identifier.urihttp://smile.stomf.bg.ac.rs/handle/123456789/1839
dc.description.abstractPurpose Gamma-glutamyl hydrolase (GGH), cyclin D1 (CCND1) and thymidylate synthase (TS) genes encode enzymes that are involved in methotrexate (MTX) action. In a group of 184 RA patients treated with MTX, we have investigated whether selected polymorphisms in these genes modulate MTX efficacy and/or have impact on adverse drug effects (ADEs). Methods The efficacy of the MTX therapy has been estimated using the disease activity score in 28 joints (DAS28-ESR) based on EULAR criteria and relative DAS28 values (rDAS28). All adverse drug events were recorded. Patients were genotyped for selected polymorphisms of the GGH (-354 G>T and 452 C>T), CCND1 (870 A>G) and TYMS (variable number of tandem repeats, VNTR, and G to C substitution of triple repeat, 3R allele) gene. Association studies have been performed between obtained genotypes and the efficacy and toxicity of MTX. Results According to the EULAR response criteria, 146 RA patients (79.3 %) were classified as responders (good/moderate response) and 38 (20.7 %) as nonresponders (poor response). Higher frequency of the TYMS 3 G/3 G genotype has been found among non-responders as compared to individuals with remaining genotypes (p=0.02). ADEs were recorded in 53 patients. Among those patients eight experienced bone marrow toxicity, all of them carried GGH -354GG genotype (p=0.003). No other significant association were observed. Conclusion The 3 G/3 G genotype of the TYMS gene may indicate predisposition of poor response to MTX and GG genotype of GGH -354 T>G polymorphism may have high predictive value for myelosuppression in RA patients.en
dc.publisherSpringer Heidelberg, Heidelberg
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175091/RS//
dc.rightsrestrictedAccess
dc.sourceEuropean Journal of Clinical Pharmacology
dc.subjectRheumatoid arthritisen
dc.subjectMethotrexateen
dc.subjectGenetic polymorphismen
dc.titleAssociation of the TYMS 3G/3G genotype with poor response and GGH 354GG genotype with the bone marrow toxicity of the methotrexate in RA patientsen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractМилић, Вера; Дамњановић, Татјана; Максимовић, Нела; Дамјанов, Немања; Радуновић, Горан; Буњевачки, Вера; Поповић, Бранка; Милашин, Јелена; Новаковић, Ивана; Крајиновић, Маја; Ковацевић, Љиљана; Луковић, Љиљана; Јекић, Биљана;
dc.citation.volume69
dc.citation.issue3
dc.citation.spage377
dc.citation.epage383
dc.citation.other69(3): 377-383
dc.citation.rankM22
dc.identifier.wos000317335200011
dc.identifier.doi10.1007/s00228-012-1341-3
dc.identifier.pmid22763757
dc.identifier.scopus2-s2.0-84877114639
dc.identifier.rcubconv_3074
dc.type.versionpublishedVersion


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record