Genotype of glutathione S-transferase and other genetic configurations in myelodysplasia

We examined polymorphisms of glutathione S-transferase (GST) genes in 159 J apanese patients with myelodysplasia and compared the incidence with that i n 43 normal individuals to clarify their pathogenetic significance in myelo dysplasia. In individuals with the GSTT1 null genotype, the odds ratios for disease risk were elevated to 2.65 (95%CI; 1.27-5.52) in de novo MDS, 4.62 (1.48-14.4) in therapy-related AML, and 2.94 (1.07-8.07) in AML with trili niage dysplasia. Other representative polymorphisms of GSTs had a similar i ncidence among patients with myelodysplasia, and those of the controls and other hematological disorders. To further investigate the genetic pathway o f myelodysplasia, the association between GST genotype and karyotype or con figurations of TP53 and NRAS was evaluated, but no relationship was noted. These results suggest that the GSTT1 null genotype may play a role in an in creased risk of myelodysplasia unrelated to other mechanisms of myelodyspla sia, such as chromosomal alterations or mutation of TP53 or NRAS. (C) 1999 Elsevier Science Ltd. All rights reserved.