GST M1 polymorphism associates with DNA oxidative damage and mortality among hemodialysis patients

Yi-Sheng Lin1, Szu-Chun Hung, Yau-Huei Wei

  • 1Division of Nephrology, Taipei City Hospital Zhongxiao Branch, Taipei, Taiwan.

Insights

Patients lacking Glutathione S-transferase M1 (GST M1) activity show increased DNA damage and a doubled mortality risk in hemodialysis. This highlights GST M1

Area of Science:

  • Nephrology
  • Genetics
  • Biochemistry

Background:

  • Leukocyte 8-hydroxy-2'-deoxyguanosine (8-OHdG) indicates DNA damage from oxidative stress in maintenance hemodialysis (MHD) patients.
  • Glutathione S-transferase M1 (GST M1) enzymes protect DNA from oxidative damage.

Purpose of the Study:

  • To investigate the association between the Glutathione S-transferase M1 (GST M1) gene polymorphism and 8-OHdG levels.
  • To determine the impact of the GST M1 gene polymorphism on all-cause mortality in MHD patients.

Main Methods:

  • Compared 8-OHdG levels and GST M1 genotype frequencies in 488 MHD patients and 372 healthy controls.
  • Utilized multivariate Cox regression to assess mortality risk associated with the GST M1(-) genotype.

Main Results:

  • The GST M1(-) genotype was linked to significantly higher leukocyte 8-OHdG levels (P < 0.001).
  • Patients with GST M1(-) genotype had approximately double the risk of all-cause mortality (HR 2.24).
  • Elevated 8-OHdG levels were observed in GST M1(-) patients with specific DNA repair gene polymorphisms or those dialyzed with cellulose membranes.

Conclusions:

  • Individuals without GST M1 activity are more susceptible to oxidative stress and face a higher mortality risk.
  • The GST M1(-) genotype is a significant risk factor for mortality in maintenance hemodialysis patients.

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