title: CDA gene polymorphisms and enzyme activity: genotype-phenotype relationship in an Italian-Caucasian population.
abstract: OBJECTIVE
  To assess the distribution of CDA activity from whole blood of 142 healthy subjects, determining its main predictors among genetic (six CDA SNPs) and physiological factors (age and gender). Moreover, we performed a kinetic study of the two CDA protein variants (Q27 and K27) determined by the rs2072671 SNP.
  
  
  METHODS
  CDA activity was assessed by HPLC. Selected CDA SNPs were genotyped by PCR-based methods. Recombinant CDA protein variants (Q27 and K27) were expressed in an Escherichia coli strain SØ5201 and kinetic assays were performed.
  
  
  RESULTS
  The mean value of CDA activity was 0.051 ± 0.024 mU/mg and followed a normal distribution in the study population. Carriers of the CDA*2B (-451T/-92G/-31Del/79C/435C) haplotype displayed higher CDA activity compared with the others. CDA -451G>A, -92A>G and 79A>C (K27Q) SNPs displayed significant associations with CDA activity. The best predictive model of CDA activity included the variables gender and CDA 79A>C (K27Q). Cytidine is the preferential substrate for the variant Q27.
  
  
  CONCLUSIONS
  We suggest the analysis of both CDA activity and CDA 79A>C (K27Q) SNP in future prospective trials with cytidine analogs, alone or in combination, in order to identify the best marker to secure the administration of these anticancer therapies.
authors: School of Biosciences & Biotechnologies, Via Gentile III da Varano, University of Camerino, 62032 Camerino, Italy.
authors: Francesco M
authors: FM
authors: Carpi
authors: Silvia
authors: S
authors: Vincenzetti
authors: Jessica
authors: J
authors: Ubaldi
authors: Stefania
authors: S
authors: Pucciarelli
authors: Valeria
authors: V
authors: Polzonetti
authors: Daniela
authors: D
authors: Micozzi
authors: Fiorenzo
authors: F
authors: Mignini
authors: Valerio
authors: V
authors: Napolioni
mesh_terms: D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*
chemical_list: D003564:Cytidine Deaminase