Association of the GSTP1 gene (Ile105Val) polymorphism with chronic myeloid leukemia.
The GSTP1 enzyme plays a key role in biotransformation and bioactivation of certain environmental pollutants such as benzo[a]pyrene-7, 8-diol-9,10-epoxide (BPDE) and other diol epoxides of polycyclic aromatic hydrocarbons. It catalyses the detoxification of base propanols that arise from DNA oxidation thus offering cellular protection against oxidative stress. A single nucleotide polymorphism at codon 105 results in the substitution of isoleucine (Ile) to valine (Val) causing a metabolically less active variant of the enzyme. We here assessed the impact of the GSTP1 codon 105 polymorphism in chronic myeloid leukemia (CML) development and therapy response. The Ile105Val polymorphism was analyzed using a PCR-RFLP technique. Two hundred and sixty patients with CML and 248 healthy, age and sex matched controls were included in the study of associations with patient characteristics and treatment outcome. The GSTP1 Ile105Val polymorphism was significantly associated with CML development (?2 = 9.57; df = 2; p = 0.0084). With respect to clinical phase, CML patients in advanced phase (accelerated and blast crisis) had higher frequency of heterozygous (Ile/Val) genotype (47.62%) compared to chronic phase (36.5%). Further 54.5% of patients in blast crisis carried valine allele as compared to those in chronic phase (36.5%). The frequency of combined genotypes (Ile/Val, Val/Val) was elevated in cytogenetic poor (41.6%) and minor (53.57%) responders as compared to major (38.51%) responders. Hence the present study suggests that GSTP1 Ile105Val polymorphism with reduced GSTP1 enzyme activity might influence CML development, progression and response rates.
Sailaja
Kagita
K
Department of Genetics, Osmania University, Hyderabad, India.
Surekha
D
D
Rao
D Nageswara
DN
Rao
D Raghunadha
DR
Vishnupriya
S
S
D000328:Adult; D001549:Benzamides; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D010879:Piperazines / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000627:therapeutic use; D012307:Risk Factors; D015996:Survival Rate; D055815:Young Adult
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D011505:Protein-Tyrosine Kinases