Association of the GSTP1 gene (Ile105Val) Polymorphism withChronic Myeloid Leukemia

Abstract

The GSTP1 enzyme plays a key role in biotransformation and bioactivation of certain environmentalpollutants such as benzo[a]pyrene-7, 8-diol-9,10-epoxide (BPDE) and other diol epoxides of polycyclic aromatichydrocarbons. It catalyses the detoxification of base propanols that arise from DNA oxidation thus offering cellularprotection against oxidative stress. A single nucleotide polymorphism at codon 105 results in the substitutionof isoleucine (Ile) to valine (Val) causing a metabolically less active variant of the enzyme. We here assessed theimpact of the GSTP1 codon 105 polymorphism in chronic myeloid leukemia (CML) development and therapyresponse. The Ile105Val polymorphism was analyzed using a PCR-RFLP technique. Two hundred and sixtypatients with CML and 248 healthy, age and sex matched controls were included in the study of associations withpatient characteristics and treatment outcome. The GSTP1 Ile105Val polymorphism was significantly associatedwith CML development (χ2 = 9.57; df = 2; p = 0.0084). With respect to clinical phase, CML patients in advancedphase (accelerated and blast crisis) had higher frequency of heterozygous (Ile/Val) genotype (47.62%) comparedto chronic phase (36.5%). Further 54.5% of patients in blast crisis carried valine allele as compared to thosein chronic phase (36.5%). The frequency of combined genotypes (Ile/Val, Val/Val) was elevated in cytogeneticpoor (41.6%) and minor (53.57%) responders as compared to major (38.51%) responders. Hence the presentstudy suggests that GSTP1 Ile105Val polymorphism with reduced GSTP1 enzyme activity might influence CMLdevelopment, progression and response rates.