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.


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.
Sutton
Joanne F
JF
Hematology Branch, NHLBI, NIH, Bethesda, MD, USA.
Stacey
Michael
M
Kearns
William G
WG
Rieg
Thomas S
TS
Young
Neal S
NS
Liu
Johnson M
JM
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
D004273:DNA, Neoplasm; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1