Background and Objective: Myelodysplastic syndromes (MDS) are clonal disorders of bone marrow stem cells characterized by ineffective hematopoiesis leading to blood cytopenia; they often progress to acute myeloid leukemia (AML). The glutathione S-transferases (GST) detoxify various agents, including those implicated in MDS. Both GSTM1 and GSTT1 genes have ‘null’ alleles and are polymorphic. We studied the impact of GTM1 and GSTT1 null genotypes on the MDS susceptibility, disease severity and laboratory indices with prognostic value for the syndrome. Material and Methods: In a hospital-based case-control study we analyzed lymphocyte DNA samples from 54 patients with MDS and 60 cancer-free controls matched for age, sex, smoking habits and origin. A multiplex polymerase chain reaction was used to genotype both GSTM1 and GSTT1 simultaneously. The χ2 test was used for statistical evaluation of the data and the odds ratios and attributable risk and population attributable risk were also calculated. Results: A significantly increased frequency of GSTM1 null genotype was found among MDS patients (57.4%) compared to controls (33.3%) (p < 0.01), while the frequency of GSTT1 null genotype was not significantly higher in MDS patients (11.1% vs. 6.66%). Neither GSTM1 and GSTT1 null genotype was associated with a particular category of the French-American-British (FAB) classification in the patients studied. Additionally, GSTM1 null genotype was associated with a significant decrease in the absolute number of neutrophils among the MDS patients. Conclusions: Individuals with GSTM1 null genotype may have increased susceptibility to MDS. Null genotypes do not seem to have be associated with FAB classification while they may be associated with putative prognostic factors.

Keywords:
Glutathione S-transferase, GSTM1, GSTT1, Myelodysplastic syndromes
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© 2001 S. Karger AG, Basel
2001
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