Association of glutathione-S-transferase gene polymorphism and lipoprotein subclasses in hemodialysis patients

Objectives

End-stage renal disease (ESRD) is characterized by profound dyslipidemia and enhanced oxidative stress. The patients also show evidence of exhausted and/or deficient anti-oxidative defense enzymes, one of them being glutathione-S-transferase (GST). This study investigates relationship between GST gene polymorphism and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses in ESRD.

Design and methods

GSTM1, T1, and P1 genotypes were determined by polymerase chain reaction–restriction fragment length polymorphism in 160 patients undergoing hemodialysis. LDL and HDL subclasses were separated by gradient gel electrophoresis and biochemical parameters were measured by routine laboratory methods.

Results

GSTM1-positive patients had higher proportion of small, dense LDL III particles than those with GSTM1-null genotype (P < 0.05). Similarly, GSTP1-Ile/Ile patients had higher proportion of LDL III (P < 0.05), but more HDL 2b and less HDL 3a particles than GSTP1-Ile/Val and Val/Val carriers (P < 0.05). LDL subclass distribution in smokers with GSTM1-null genotype was shifted towards smaller particles, as compared to GSTM1-positive and GSTM1-null non-smokers. Smokers with GSTP1-Ile/Val and Val/Val genotypes had smaller LDL size than their non-smoking counterparts (P < 0.05). Both smokers and non-smokers with GSTP1 Ile/Ile genotype had more LDL III particles than non-smokers carrying Val allele. Non-smokers with GSTP1 Ile/Ile genotype had more HDL 2b subclasses than non-smokers with GSTP1-Ile/Val and Val/Val (P < 0.05), but less HDL 3a particles than smokers with GSTP1-Ile/Val and Val/Val genotypes (P < 0.05). GSTT1 gene polymorphism had no effect on lipoprotein subclass distributions.

Conclusions

Our results demonstrate significant associations between low activity GST genotypes and proatherogenic lipoprotein particles in hemodialysis patients which might further increase their cardiovascular disease risk.