title: [Study on the relationship between human cytidine deaminase gene polymorphisms and Ara-C sensitivity].
abstract: OBJECTIVE
  To study the relationship between coding single-nucleotide polymorphisms (cSNPs) in the human cytidine deaminase (CDA) gene and cytosine arabinoside (Ara-C) sensitivity in childhood acute leukemia (AL).
  
  
  METHODS
  cDNAs from 87 leukemia and 199 control blood samples were analyzed for the cSNPs in CDA by PCR-denaturing gradient gel electrophoresis (DGGE) and sequencing. Human CDA genes were transformed into E. coli and yeast, respectively. Catalytic activities of the allele CDA and variant CDAs were determined by HPLC assay. The Ara-C sensitivity of the yeast transformants was measured by growth inhibition assays.
  
  
  RESULTS
  Three known different polymorphisms, namely, 79A/C (K27Q), 208G/A (A70T) and 435T/C (silent) were identified in the coding region of CDA from an investigated Chinese population and displayed allelic frequencies of 12.1%, 0.5% and 76.2%, respectively. No association with susceptibility to disease was observed. Compared with that of CDA70A, the deamination activities for cytidine and Ara-C substrates of the E. coli transformants carrying human CDA70T were decreased by 53% and 63%, respectively (P<0.01), and the Ara-C IC50 value of the yeast transformants was also significantly decreased by 25% [(973 +/- 61) micromol/L to (735 +/- 31) micromol/L, P<0.05].
  
  
  CONCLUSIONS
  The 3 known cSNPs and their allelic frequencies of CDA are identified in a Chinese childhood AL. The 208A genotype is shown to be more sensitive to Ara-C than 208G genotype.
authors.affiliation: Institute of Pediatrics, Shenzhen Children's Hospital, Shenzhen 518026, China.
authors.forename: Xiao-wen
authors.initials: XW
authors.lastname: Chen
authors.forename: Li-jie
authors.initials: LJ
authors.lastname: Yue
authors.forename: Cheng-rong
authors.initials: CR
authors.lastname: Li
authors.forename: Chang-gang
authors.initials: CG
authors.lastname: Li
authors.forename: Hong-song
authors.initials: HS
authors.lastname: Shi
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
mesh_terms: D003561:Cytarabine / Q000627:therapeutic use*; D003564:Cytidine Deaminase / Q000235:genetics*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D003561:Cytarabine; D003564:Cytidine Deaminase