SEARCH:   Advanced

Blood, 5 March 2009, Vol. 113, No. 10, pp. 2145-2153. Prepublished online as a Blood First Edition Paper on December 24, 2008; DOI 10.1182/blood-2008-05-154302. This Article Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2008-05-154302v1 113/10/2145    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hartford, C. M. Articles by Dolan, M. E. Search for Related Content PubMed PubMed Citation Articles by Hartford, C. M. Articles by Dolan, M. E. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 7, 2008 Accepted December 16, 2008 Population specific genetic variants important in susceptibility to cytarabine arabinoside cytotoxicity Christine M. Hartford, Shiwei Duan, Shannon M. Delaney, Shuangli Mi, Emily O. Kistner, Jatinder K. Lamba, R. Stephanie Huang, and M. Eileen Dolan* Department of Pediatrics, University of Chicago, Chicago, IL, United States Department of Medicine, University of Chicago, Chicago, IL, United States Department of Health Studies, University of Chicago, Chicago, IL, United States Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, United States * Corresponding author; email: edolan{at}medicine.bsd.uchicago.edu. Cytarabine arabinoside (ara-C) is an antimetabolite used to treat hematologic malignancies. Resistance is a common reason for treatment failure with adverse side effects contributing to morbidity and mortality. Identification of genetic factors important in susceptibility to ara-C cytotoxicity may allow for individualization of treatment. We employed an unbiased whole genome approach using lymphoblastoid cell lines derived from individuals of European (CEU) or African (YRI) ancestry to identify these genetic factors. We interrogated more than 2 million single nucleotide polymorphisms (SNPs) for association with susceptibility to ara-C and narrowed our focus by concentrating on SNPs that affected gene expression. We identified a unique pharmacogenetic signature consisting of 4 SNPs explaining 51% of the variability in sensitivity to ara-C among the CEU and 5 SNPs explaining 58% of the variation among the YRI. Population-specific signatures were secondary to either: 1) Polymorphic SNPs in one population but monomorphic in the other; 2) Significant associations of SNPs with cytotoxicity or gene expression in one population but not the other. We validated the gene expression-cytotoxicity relationship for a subset of genes in a separate group of lymphoblastoid cell lines. These unique genetic signatures comprise novel genes that can now be studied further in functional studies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. H. O'Donnell and M. E. Dolan Cancer Pharmacoethnicity: Ethnic Differences in Susceptibility to the Effects of Chemotherapy Clin. Cancer Res., August 1, 2009; 15(15): 4806 - 4814. [Abstract] [Full Text] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020