The role of the glutathione S-transferase genes GSTT1, GSTM1, and GSTP1 in acetaminophen-poisoned patients

TY - JOUR

T1 - The role of the glutathione S-transferase genes GSTT1, GSTM1, and GSTP1 in acetaminophen-poisoned patients

AU - Buchard, Anders

AU - Eefsen, Martin

AU - Semb, Synne

AU - Andersen, Stig Ejdrup

AU - Morling, Niels

AU - Bendtsen, Flemming

AU - Larsen, Fin Stolze

AU - Dalhoff, Kim

PY - 2012/1

Y1 - 2012/1

N2 - 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.

AB - 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.

KW - Acetaminophen

KW - Adult

KW - Female

KW - Gene Deletion

KW - Genes

KW - Genotype

KW - Glutathione S-Transferase pi

KW - Glutathione Transferase

KW - Homozygote

KW - Humans

KW - Male

KW - Middle Aged

KW - Overdose

KW - Polymorphism, Genetic

KW - Prothrombin Time

KW - Risk Factors

U2 - 10.3109/15563650.2011.639713

DO - 10.3109/15563650.2011.639713

M3 - Journal article

C2 - 22175791

SN - 1556-9519

VL - 50

SP - 27

EP - 33

JO - Clinical toxicology (Philadelphia, Pa.)

JF - Clinical toxicology (Philadelphia, Pa.)

IS - 1

ER -