Association of CYP3A5FNx013 polymorphism with development of acute leukemia

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 (CYP3A5FNx013). We investigated the...

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Bibliographic Details
Published in:Indian journal of human genetics 2011-09, Vol.17 (3), p.175
Main Authors: Rao, D, Manjula, G, Sailaja, K, Surekha, D, Raghunadharao, D, Rajappa, Senthil, Vishnupriya, S
Format: Article
Language:English
Subjects:
Acute leukemia
Carcinogens
Diagnosis
Enzymes
Genetic aspects
Genotype & phenotype
Leukemia
Metabolites
Polymorphism
Risk factors
Single nucleotide polymorphisms
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Summary: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 (CYP3A5FNx013). We investigated the association between CYP3A5FNx013 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 CYP3A5FNx013 polymorphism using PCR-RFLP method. Statistical analysis was performed with SPSS version (15.0) to detect the association between CYP3A5FNx013 polymorphism and acute leukemia. Results : The CYP3A5FNx013 polymorphism 3/3 genotype was significantly associated with acute leukemia development (χ2 - 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 CYP3A5FNx013 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.
ISSN:0971-6866
1998-362X
DOI:10.4103/0971-6866.92098