title: Association of CYP3A5*3 polymorphism with development of acute leukemia.
abstract: BACKGROUND
  CYP3A5 was observed to be an important genetic contributor to inter individual differences in CYP3A-dependent drug metabolism in acute leukemic patients. Loss of CYP3A5 expression was mainly conferred by a single nucleotide polymorphism at 6986A>G (CYP3A5*3). We investigated the association between CYP3A5*3 polymorphism and acute leukemia.
  
  
  METHODS
  Two hundred and eighty nine acute leukemia cases comprising of 145 acute lymphocytic leukemia (ALL), 144 acute myeloid leukemia and 241 control samples were analyzed for CYP3A5*3 polymorphism using PCR-RFLP method. Statistical analysis was performed with SPSS version (15.0) to detect the association between CYP3A5*3 polymorphism and acute leukemia.
  
  
  RESULTS
  The CYP3A5*3 polymorphism 3/3 genotype was significantly associated with acute leukemia development (χ(2)- 133.53; df-2, P 0.000). When the data was analyzed with respect to clinical variables, mean WBC, blast % and LDH levels were increased in both ALL and AML cases with 3/3 genotype. The epidemiological variables did not contribute to the genotype risk to develop either AML or ALL.
  
  
  CONCLUSIONS
  The results suggest that the CYP3A5*3 polymorphism might confer the risk to develop ALL or AML emphasizing the significance of effective phase I detoxification in carcinogenesis. Association of the polymorphism with clinical variables indicate that the 3/3 genotype might also contribute to poorer survival of the patients.
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, India.
authors.forename: D Nageswara
authors.initials: DN
authors.lastname: Rao
authors.forename: G
authors.initials: G
authors.lastname: Manjula
authors.forename: K
authors.initials: K
authors.lastname: Sailaja
authors.forename: D
authors.initials: D
authors.lastname: Surekha
authors.forename: D
authors.initials: D
authors.lastname: Raghunadharao
authors.forename: Senthil
authors.initials: S
authors.lastname: Rajappa
authors.forename: S
authors.initials: S
authors.lastname: Vishnupriya