Increased Risk for Aplastic Anemia and Myelodysplastic Syndrome in Individuals Lacking Glutathione S-Transferase Genes

BACKGROUND: Aplastic anemia (AA) and myelodysplastic syndrome (MDS) are marrow failure states that may be associated with chromosomal instability. An absence of the glutathione S-transferase (GST) enzyme may genetically predispose individuals to AA or MDS. PROCEDURE AND RESULTS: To test this hypothesis, we determined the GSTM1 and GSTT1 genotypes in a total of 196 patients using multiplex PCR. The GSTT1 null genotype was found to be overrepresented in Caucasian, Asian, and Hispanic patients with either AA or MDS. We confirmed a difference in the expected frequency of the GSTM1 null genotype in Caucasian MDS patients. The double null GSTM1/GSTT1 genotype was also overrepresented in Caucasian AA and MDS patients. In our population, 26% of AA patients and 40% of MDS patients had a chromosomal abnormality identified by karyotype or FISH analyses for chromosomes 7 and 8. Patients with AA and the GSTT1 null genotype had an increased frequency of chromosomal abnormalities (P = 0.003). CONCLUSION: There seems to be an increased risk for AA and MDS in individuals lacking GSTT1 or both GSTM1/GSTT1