title: Increased risk for aplastic anemia and myelodysplastic syndrome in individuals lacking glutathione S-transferase genes.
abstract: 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.
  
  
  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).
  
  
  CONCLUSIONS
  There seems to be an increased risk for AA and MDS in individuals lacking GSTT1 or both GSTM1/GSTT1.
authors.affiliation: Hematology Branch, NHLBI, NIH, Bethesda, MD, USA.
authors.forename: Joanne F
authors.initials: JF
authors.lastname: Sutton
authors.forename: Michael
authors.initials: M
authors.lastname: Stacey
authors.forename: William G
authors.initials: WG
authors.lastname: Kearns
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Rieg
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
authors.forename: Johnson M
authors.initials: JM
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000741:Anemia, Aplastic / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D012307:Risk Factors
chemical_list: D004273:DNA, Neoplasm; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1