Medknow Publications on behalf of Indian Society of Human Genetics
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. Materials and 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 (\u3c72 - 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. Conclusion : 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