GST M1 polymorphism associates with DNA oxidative damage and mortality among hemodialysis patients.
Leukocyte 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a surrogate marker of oxidant-induced DNA damage in patients undergoing maintenance hemodialysis (MHD). Glutathione S-transferase M1 (GST M1) is a member of the GST family of proteins, which protect cellular DNA against oxidative damage. This study tested the association of a common GST M1 gene polymorphism [GST M1(-)], known to produce a dysfunctional enzyme, with levels of 8-OHdG in peripheral blood leukocytes and all-cause mortality among MHD patients. Among 488 MHD patients and 372 gender-matched healthy subjects, the frequency of the GST M1(-) genotype was 63.1 and 60.2%, respectively. The GST M1(-) genotype was associated with significantly higher levels of leukocyte 8-OHdG compared with the GST M1(+) genotype, even after adjustment for potential confounders (P < 0.001). Moreover, GST M1(-) patients who also had a common polymorphism in the DNA repair enzyme 8-oxoguanine DNA glycosylase 1 or who underwent dialysis with a bioincompatible cellulose membrane had the highest median levels of leukocyte 8-OHdG. Multivariate Cox regression revealed that among MHD patients, GST M1(-) genotype approximately doubled the risk for all-cause mortality (hazard ratio 2.24; 95% confidence interval 1.30 to 4.51) during the mean follow-up of 34 mo. In conclusion, patients without GST M1 activity are more vulnerable to oxidative stress and are at greater risk for death compared with those who possess GST M1 activity.
Lin
Yi-Sheng
YS
Division of Nephrology, Taipei City Hospital Zhongxiao Branch, Taipei, Taiwan.
Hung
Szu-Chun
SC
Wei
Yau-Huei
YH
Tarng
Der-Cherng
DC
D000368:Aged; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D006435:Renal Dialysis
D045647:DNA Glycosylases; D005982:Glutathione Transferase; C479058:oxoguanine glycosylase 1, human