title: The role of the glutathione S-transferase genes GSTT1, GSTM1, and GSTP1 in acetaminophen-poisoned patients.
abstract: The aim of this study was to assess if genetic variants in the glutathione-S-transferase genes GST-T1, M1, and P1 reflect risk factors in acetaminophen (APAP)-poisoned patients assessed by investigation of the relation to prothrombin time (PT), which is a sensitive marker of survival in these patients. A total of 104 APAP-poisoned patients were genotyped for deletion polymorphisms in the GSTT1 and GSTM1 genes and for the GSTP1 Ile105Val polymorphism. We found a borderline association (p = 0.05) between the GSTT1 homozygous deletion genotype and high trough PT (a marker of prognosis in APAP poisoning) compared to carrying two functioning copies of the gene. No significant association was found between any of the GSTM1 and GSTP1 genotypes and PT. The frequency of GSTP1 Val/Val genotypes was significantly lower in the patients than in the background population (p = 0.047). The results suggest that the GSTT1 homozygous deletion genotype may be associated with a better prognosis after APAP poisoning and that carriers of the GSTP1 homozygous variant genotype may have a decreased risk of being APAP poisoned.
authors.affiliation: Department of Forensic Medicine, University of Copenhagen, Copenhagen, Denmark. kdal0006@bbh.regionh.dk
authors.forename: Anders
authors.initials: A
authors.lastname: Buchard
authors.forename: Martin
authors.initials: M
authors.lastname: Eefsen
authors.forename: Synne
authors.initials: S
authors.lastname: Semb
authors.forename: Stig Ejdrup
authors.initials: SE
authors.lastname: Andersen
authors.forename: Niels
authors.initials: N
authors.lastname: Morling
authors.forename: Flemming
authors.initials: F
authors.lastname: Bendtsen
authors.forename: Fin Stolze
authors.initials: FS
authors.lastname: Larsen
authors.forename: Kim
authors.initials: K
authors.lastname: Dalhoff
mesh_terms: D000082:Acetaminophen / Q000378:metabolism / Q000506:poisoning*; D000328:Adult; D062787:Drug Overdose / Q000201:enzymology / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005796:Genes / Q000235:genetics; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011517:Prothrombin Time; D012307:Risk Factors
chemical_list: D000082:Acetaminophen; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human