Increased frequencies of glutathione-S transferase (GSTT1 and GSTMA) null genotypes in Korean patients with acquired aplastic anemia

Kyung A. Lee, Sun Hee Kirn, Young Joon Hong

Research output: Contribution to journalArticle

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Abstract

Background: The etiology of aplastic anemia (AA) may be multifactorial and toxic environmental factors have been postulated to contribute to the etiology of AA. It is possible that patients with reduced ability to metabolize environmental carcinogens or toxins are at risk for developing AA. The (GSTM1) and (GSTT1) members of the glutathione S-transferase multigene family are polymorphic in human beings and have been implicated in detoxifying mutagenic electrophilic compounds. An increased frequency of OST null genotypes has been associated with several malignancies. We studied whether the homogygous null genotypes of GSTM1 and GSTT1 would alter the risk for AA and the relationship of the GST genotype to the chromosomal abnormalities in AA patients to clarify the multistep pathogenesis of AA based on this possible genetic predisposition. Methods: We analyzed bone marrow samples from 57 AA patients and peripheral blood samples from 75 healty controls of similar age and sex. Multiplex PCR was performed on extracted DNA to co-amplify the GSTM1 and GSTT1 alleles, and CYP1A1 as an internal control. Results: The GSTM1 null genotype was found in 47/57 (82.5%) AA patients and 45/75 (60.0%) controls. The GSTT1 null genotype was found in 41/57 (71.9%) and 34/75 (45.3%) controls. Most of the AA patients showed GSTM1 null genotype [odds ratio (OR) : 3.1, 95% confidence interval (CI), 1.4-7.1, P=0.01). The incidence of GSTT1 null genotype was also significantly higher [OR : 3.1, 95% CI, 1.5-6.4, P=0.004] for AA patients. Of the 57 AA patients, 9 patients(15.8%) had chromosomal abnormalities at the time of diagnosis. And, all the AA patients with chromosomal abnormalities showed GSTT1 null genotype(P=0.05). Conclusions: The frequencies of GSTM1 and GSTT1 null genotypes are significantly higher in Korean AA patients. Especially, genetic instability or chromosomal damage due to abnormal detoxification of environmental or endogenous toxins might be important pathophysiologic mechanism of AA in the patients with GSTT1 null genotype.

Original languageEnglish
JournalBlood
Volume96
Issue number11 PART I
Publication statusPublished - 2000 Dec 1

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Aplastic Anemia
Genotype
Environmental Carcinogens
Detoxification
Cytochrome P-450 CYP1A1
Poisons
Glutathione Transferase
Chromosome Aberrations
Bone
Blood
glutathione S-transferase T1
DNA
Odds Ratio
Confidence Intervals
Chromosomal Instability
Multiplex Polymerase Chain Reaction
Genetic Predisposition to Disease
Multigene Family

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

@article{6a2c509cba6240a7880ed356bcc9929e,
title = "Increased frequencies of glutathione-S transferase (GSTT1 and GSTMA) null genotypes in Korean patients with acquired aplastic anemia",
abstract = "Background: The etiology of aplastic anemia (AA) may be multifactorial and toxic environmental factors have been postulated to contribute to the etiology of AA. It is possible that patients with reduced ability to metabolize environmental carcinogens or toxins are at risk for developing AA. The (GSTM1) and (GSTT1) members of the glutathione S-transferase multigene family are polymorphic in human beings and have been implicated in detoxifying mutagenic electrophilic compounds. An increased frequency of OST null genotypes has been associated with several malignancies. We studied whether the homogygous null genotypes of GSTM1 and GSTT1 would alter the risk for AA and the relationship of the GST genotype to the chromosomal abnormalities in AA patients to clarify the multistep pathogenesis of AA based on this possible genetic predisposition. Methods: We analyzed bone marrow samples from 57 AA patients and peripheral blood samples from 75 healty controls of similar age and sex. Multiplex PCR was performed on extracted DNA to co-amplify the GSTM1 and GSTT1 alleles, and CYP1A1 as an internal control. Results: The GSTM1 null genotype was found in 47/57 (82.5{\%}) AA patients and 45/75 (60.0{\%}) controls. The GSTT1 null genotype was found in 41/57 (71.9{\%}) and 34/75 (45.3{\%}) controls. Most of the AA patients showed GSTM1 null genotype [odds ratio (OR) : 3.1, 95{\%} confidence interval (CI), 1.4-7.1, P=0.01). The incidence of GSTT1 null genotype was also significantly higher [OR : 3.1, 95{\%} CI, 1.5-6.4, P=0.004] for AA patients. Of the 57 AA patients, 9 patients(15.8{\%}) had chromosomal abnormalities at the time of diagnosis. And, all the AA patients with chromosomal abnormalities showed GSTT1 null genotype(P=0.05). Conclusions: The frequencies of GSTM1 and GSTT1 null genotypes are significantly higher in Korean AA patients. Especially, genetic instability or chromosomal damage due to abnormal detoxification of environmental or endogenous toxins might be important pathophysiologic mechanism of AA in the patients with GSTT1 null genotype.",
author = "Lee, {Kyung A.} and Kirn, {Sun Hee} and Hong, {Young Joon}",
year = "2000",
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Increased frequencies of glutathione-S transferase (GSTT1 and GSTMA) null genotypes in Korean patients with acquired aplastic anemia. / Lee, Kyung A.; Kirn, Sun Hee; Hong, Young Joon.

In: Blood, Vol. 96, No. 11 PART I, 01.12.2000.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Increased frequencies of glutathione-S transferase (GSTT1 and GSTMA) null genotypes in Korean patients with acquired aplastic anemia

AU - Lee, Kyung A.

AU - Kirn, Sun Hee

AU - Hong, Young Joon

PY - 2000/12/1

Y1 - 2000/12/1

N2 - Background: The etiology of aplastic anemia (AA) may be multifactorial and toxic environmental factors have been postulated to contribute to the etiology of AA. It is possible that patients with reduced ability to metabolize environmental carcinogens or toxins are at risk for developing AA. The (GSTM1) and (GSTT1) members of the glutathione S-transferase multigene family are polymorphic in human beings and have been implicated in detoxifying mutagenic electrophilic compounds. An increased frequency of OST null genotypes has been associated with several malignancies. We studied whether the homogygous null genotypes of GSTM1 and GSTT1 would alter the risk for AA and the relationship of the GST genotype to the chromosomal abnormalities in AA patients to clarify the multistep pathogenesis of AA based on this possible genetic predisposition. Methods: We analyzed bone marrow samples from 57 AA patients and peripheral blood samples from 75 healty controls of similar age and sex. Multiplex PCR was performed on extracted DNA to co-amplify the GSTM1 and GSTT1 alleles, and CYP1A1 as an internal control. Results: The GSTM1 null genotype was found in 47/57 (82.5%) AA patients and 45/75 (60.0%) controls. The GSTT1 null genotype was found in 41/57 (71.9%) and 34/75 (45.3%) controls. Most of the AA patients showed GSTM1 null genotype [odds ratio (OR) : 3.1, 95% confidence interval (CI), 1.4-7.1, P=0.01). The incidence of GSTT1 null genotype was also significantly higher [OR : 3.1, 95% CI, 1.5-6.4, P=0.004] for AA patients. Of the 57 AA patients, 9 patients(15.8%) had chromosomal abnormalities at the time of diagnosis. And, all the AA patients with chromosomal abnormalities showed GSTT1 null genotype(P=0.05). Conclusions: The frequencies of GSTM1 and GSTT1 null genotypes are significantly higher in Korean AA patients. Especially, genetic instability or chromosomal damage due to abnormal detoxification of environmental or endogenous toxins might be important pathophysiologic mechanism of AA in the patients with GSTT1 null genotype.

AB - Background: The etiology of aplastic anemia (AA) may be multifactorial and toxic environmental factors have been postulated to contribute to the etiology of AA. It is possible that patients with reduced ability to metabolize environmental carcinogens or toxins are at risk for developing AA. The (GSTM1) and (GSTT1) members of the glutathione S-transferase multigene family are polymorphic in human beings and have been implicated in detoxifying mutagenic electrophilic compounds. An increased frequency of OST null genotypes has been associated with several malignancies. We studied whether the homogygous null genotypes of GSTM1 and GSTT1 would alter the risk for AA and the relationship of the GST genotype to the chromosomal abnormalities in AA patients to clarify the multistep pathogenesis of AA based on this possible genetic predisposition. Methods: We analyzed bone marrow samples from 57 AA patients and peripheral blood samples from 75 healty controls of similar age and sex. Multiplex PCR was performed on extracted DNA to co-amplify the GSTM1 and GSTT1 alleles, and CYP1A1 as an internal control. Results: The GSTM1 null genotype was found in 47/57 (82.5%) AA patients and 45/75 (60.0%) controls. The GSTT1 null genotype was found in 41/57 (71.9%) and 34/75 (45.3%) controls. Most of the AA patients showed GSTM1 null genotype [odds ratio (OR) : 3.1, 95% confidence interval (CI), 1.4-7.1, P=0.01). The incidence of GSTT1 null genotype was also significantly higher [OR : 3.1, 95% CI, 1.5-6.4, P=0.004] for AA patients. Of the 57 AA patients, 9 patients(15.8%) had chromosomal abnormalities at the time of diagnosis. And, all the AA patients with chromosomal abnormalities showed GSTT1 null genotype(P=0.05). Conclusions: The frequencies of GSTM1 and GSTT1 null genotypes are significantly higher in Korean AA patients. Especially, genetic instability or chromosomal damage due to abnormal detoxification of environmental or endogenous toxins might be important pathophysiologic mechanism of AA in the patients with GSTT1 null genotype.

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