title: ABCC1 polymorphisms in anthracycline-induced cardiotoxicity in childhood acute lymphoblastic leukaemia.
abstract: Anthracyclines are potent cytostatic drugs, the correct dosage being critical to avoid possible cardiac side effects. ABCC1 [ATP-binding cassette, sub-family C, member 1; also denoted as MRP1 (multidrug resistance-associated protein 1)] is expressed in the heart and takes part in the detoxification and protection of cells from the toxic effects of xenobiotics, including anthracyclines. Our objective was to search for associations between LV (left ventricular) function and single-nucleotide polymorphisms of the ABCC1 gene in children receiving anthracycline chemotherapy. Data of 235 paediatric patients with acute lymphoblastic leukaemia was analysed. Patients were followed-up by echocardiography (median follow-up 6.3 years). Nine polymorphisms in the ABCC1 gene were genotyped. The ABCC1 rs3743527TT genotype and rs3743527TT–rs246221TC/TT genotype combination were associated with lower LVFS (left ventricular fractional shortening) after chemotherapy. The results suggest that genetic variants in the ABCC1 gene influence anthracycline-induced LV dysfunction.
authors.affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
authors.forename: Agnes F
authors.initials: AF
authors.lastname: Semsei
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Erdelyi
authors.forename: Ildiko
authors.initials: I
authors.lastname: Ungvari
authors.forename: Edit
authors.initials: E
authors.lastname: Csagoly
authors.forename: Marta Z
authors.initials: MZ
authors.lastname: Hegyi
authors.forename: Petra S
authors.initials: PS
authors.lastname: Kiszel
authors.forename: Orsolya
authors.initials: O
authors.lastname: Lautner-Csorba
authors.forename: Judit
authors.initials: J
authors.lastname: Szabolcs
authors.forename: Peter
authors.initials: P
authors.lastname: Masat
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Fekete
authors.forename: Andras
authors.initials: A
authors.lastname: Falus
authors.forename: Csaba
authors.initials: C
authors.lastname: Szalai
authors.forename: Gabor T
authors.initials: GT
authors.lastname: Kovacs
mesh_terms: D000293:Adolescent; D000483:Alleles; D018943:Anthracyclines; D002648:Child; D002675:Child, Preschool; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006352:Heart Ventricles / Q000000981:diagnostic imaging; D006801:Humans; D007223:Infant; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000139:chemically induced* / Q000235:genetics*; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D018943:Anthracyclines; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C421109:multidrug resistance-associated protein 1