[Study on the relationship between human cytidine deaminase gene polymorphisms and Ara-C sensitivity].
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.
Chen
Xiao-wen
XW
Institute of Pediatrics, Shenzhen Children's Hospital, Shenzhen 518026, China.
Yue
Li-jie
LJ
Li
Cheng-rong
CR
Li
Chang-gang
CG
Shi
Hong-song
HS
Zhang
Min
M
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
D003561:Cytarabine; D003564:Cytidine Deaminase