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Glutathione S‐transferase gene polymorphic sequence variations: Association with risk and response to Imatinib among Chronic Myeloid Leukemia patients of Kashmir
Author(s) -
Baba Shahid M.,
Shah Zafar A.,
Pandith Arshad A.,
Geelani Sajad A.,
Mir Mohammad M.,
Bhat Javid R.,
Gul Ayaz,
Bhat Gul M.
Publication year - 2021
Publication title -
international journal of laboratory hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.705
H-Index - 55
eISSN - 1751-553X
pISSN - 1751-5521
DOI - 10.1111/ijlh.13471
Subject(s) - gstp1 , genotype , glutathione s transferase , imatinib , myeloid leukemia , biology , single nucleotide polymorphism , medicine , chronic myelogenous leukemia , immunology , gene , microbiology and biotechnology , genetics , gastroenterology , glutathione , leukemia , enzyme , biochemistry
Abstract Introduction Glutathione S‐transferase (GST) gene deletion or polymorphic sequence variations lead to decreased enzyme activity that influences susceptibility and response to tyrosine kinase inhibitors in chronic myeloid leukemia (CML). We aimed to analyze relation of different GST gene sequence variants with susceptibility and response to Imatinib in CML. Material and Methods A total of 150 CML cases and equal number of age and gender matched healthy controls were genotyped for five GST polymorphisms by multiplex‐PCR and PCR‐RFLP techniques. BCR‐ABL1 transcripts were quantified by quantitative Real Time PCR (qRT‐PCR). Results GSTT1 , GSTO1, and GSTO2 SNPs revealed no association, while as GSTM1 null genotype was observed to protect against the development of CML (OR = 0.53, P = .01). GSTP1 variant genotypes AG (OR = 2.1, P = .003) and GG (OR = 5.6, P < .001), significantly associated with increased risk of CML. Combined genotype analysis showed protective impact of GSTT1 present / GSTM1 null (OR = 0.44, P = .003) while as GSTT1 present / GSTP1‐ GG (OR = 6.92, P < .001) and GSTM1 present / GSTP1‐ GG (OR = 6.33, P < .001), significantly increased CML risk. GSTM1 null genotype individually and in combination with GSTT1 present associated with superior rate of major molecular response (MMR) and event free survival (EFS) (log‐rank P = .029). GSTO2‐ AG+GG genotype associated with significantly inferior MMR rates at 3, 6, and 12 months. Also, patients with GSTO2‐ GG genotype showed significantly reduced EFS (log‐rank P = .025). Multivariate analysis confirmed GSTM1 null as a better (HR:0.19, P = .029) and GSTO2 ‐GG genotype as an independent poor prognostic factor (HR:2.29, P = .037). Conclusion GSTM1 null genotype seems to have a better prognostic role while GSTP1 variants significantly increase CML risk. Also, results support a correlation between disease outcome and GSTO2 polymorphism.