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Cytidine deaminase polymorphisms and worse treatment response in normal karyotype AML

Title
Cytidine deaminase polymorphisms and worse treatment response in normal karyotype AML
Authors
Hyo Kim L.Sub Cheong H.Koh Y.Ahn K.-S.Lee C.Kim H.-L.Doo Shin H.Yoon S.-S.
Ewha Authors
김형래
SCOPUS Author ID
김형래scopus
Issue Date
2015
Journal Title
Journal of Human Genetics
ISSN
1434-5161JCR Link
Citation
vol. 60, no. 12, pp. 749 - 754
Publisher
Nature Publishing Group
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
The cytidine deaminase (CDA) catalyzes the irreversible hydrolytic deamination of the cytarabine (AraC) into a 1-β-D-Arabinofuranosyluracil (AraU), an inactive metabolite that plays a crucial role in lowering the amount of AraC, a key chemotherapeutic drug, in the treatment of patients with acute myeloid leukemia (AML). In this study, we hypothesized that CDA polymorphisms were associated with the AraC metabolism for AML treatment and/or related clinical phenotypes. We analyzed 16 polymorphisms of CDA among 50 normal karyotype AML (NK-AML) patients, 45 abnormal karyotype AML (AK-AML) patients and 241 normal controls (NC). Several polymorphisms and haplotypes, rs532545, rs2072671, rs471760, rs4655226, rs818194 and CDA-ht3, were found to have a strong correlation with NK-AML compared with NC and these polymorphisms also revealed strong linkage disequilibrium with each other. Among them, rs2072671 (79A>C), which is located in a coding region and the resultant amino acid change K27Q, showed significant associations with NK-AML compared with NC (P=0.009 and odds ratio=2.44 in the dominant model). The AC and CC genotypes of rs2072671 (79A>C) were significantly correlated with shorter overall survival rates (P=0.03, hazard ratio=1.84) and first complete remission duration (P=0.007, hazard ratio=3.24) compared with the AA genotype in the NK-AML patients. Our results indicate that rs2072671 in CDA may be an important prognostic marker in NK-AML patients. © 2015 The Japan Society of Human Genetics All rights reserved.
DOI
10.1038/jhg.2015.105
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의학전문대학원 > 의학과 > Journal papers
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