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Cell Biology International (2012) 36, 79–86 (Printed in Great Britain)

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ABCC1 polymorphisms in anthracycline-induced cardiotoxicity in childhood acute lymphoblastic leukaemia

Agnes F. Semsei*, Daniel J. Erdelyi*†, Ildiko Ungvari*, Edit Csagoly*, Marta Z. Hegyi†, Petra S. Kiszel*, Orsolya Lautner‑Csorba*, Judit Szabolcs†, Peter Masat‡, Gyorgy Fekete†, Andras Falus*, Csaba Szalai^1§¶‖ and Gabor T. Kovacs†

*Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary, †Second Department of Pediatrics, Semmelweis University, Budapest, Hungary, ‡Markusovszky Hospital of Vas County Council, Szombathely, Hungary, §Heim Pal Children Hospital, Budapest, Hungary, ¶Inflammation Biology and Immunogenomics Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary, and ‖Csertex Research Laboratory, Budapest, Hungary

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.

Key words: ABCC1, cardiotoxicity, fractional shortening, leukaemia, pharmacogenetics, side effects

Abbreviations: ABC, ATP-binding cassette, ABCC1, ABC, sub-family C, member 1, ALL, acute lymphoblastic leukaemia, BFM, Berlin–Frankfurt–Münster, ECHO, echocardiography, HWE, Hardy–Weinberg equilibrium, LV, left ventricular, LVEDD, left ventricular end-diastolic-dimension, LVESD, left ventricular end-systolic dimension, LVFS, left ventricular fractional shortening, MRP1, multidrug resistance-associated protein 1, NHL, non-Hodgkin lymphoma, SNP, single-nucleotide polymorphism, 3′-UTR, 3′-untranslated region

¹To whom correspondence should be addressed (email genomika.cs@gmail.com).

Received 2 May 2011/7 July 2011; accepted 20 September 2011

Published as Cell Biology International Immediate Publication 20 September 2011, doi:10.1042/CBI20110264

© The Author(s) Journal compilation © 2012 Portland Press Limited