[Single-nucleotide polymorphisms of the cytidine deaminase gene in childhood with acute leukemia and normal Chinese children].
OBJECTIVE
Cytidine deaminase (CDA) is a key enzyme for metabolizing chemotherapeutic agent cytosine arabinoside (Ara-C), a deoxycytidine analog used for treatment of acute leukemia and lymphomas. Significant variability in the antitumor efficacy and systemic toxicity of Ara-C has been observed in cancer patients. Two missense mutations changing Ara-C sensitivity and toxicity had been found in the human CDA. Coding single-nucleotide polymorphisms (cSNPs) of CDA had been investigated in Japanese, Europeans Africans and Americans, but not in Chinese. The purpose of this study was to survey the allelic frequencies of CDA cSNPs in Chinese children.


METHODS
The bone marrow samples from 87 childhood patients with acute leukemia and peripheral blood samples from 199 non-malignancy-bearing children were obtained to prepare complementary DNAs (cDNAs). The cDNAs were analyzed for the polymorphisms in CDA by polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE), PCR-restriction fragment length polymorphism (RFLP) and direct-sequencing. The distributive difference of each genotype was evaluated between children with acute leukemia and control children.


RESULTS
Three known different polymorphisms, namely, 79A to C (K27Q), 208G to A (A70T) and 435T to C (silent) were identified in the coding region of CDA from the investigated Chinese population and displayed allelic frequencies of 12.1%, 0.52% and 76.2%, respectively. No association with susceptibility to disease was observed.


CONCLUSIONS
This study demonstrates 3 cSNPs and their allelic frequencies of CDA in Chinese children, and provides the first step to identify genetic markers for predicting variability in Ara-C response and toxicity.
Yue
Li-jie
LJ
Pediatrics Institute of Shenzhen Children's Hospital, Shenzhen, Guangdong, 518026 P. R. China. lijieyue@yahoo.com.
Chen
Xiao-wen
XW
Li
Cheng-rong
CR
Li
Chang-gang
CG
Shi
Hong-song
HS
Zhang
Min
M
D000208:Acute Disease; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003564:Cytidine Deaminase / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007938:Leukemia / Q000235:genetics* / Q000473:pathology; D008297:Male; D020641:Polymorphism, Single Nucleotide
D003564:Cytidine Deaminase