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

Abstract

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.

Keywords: Cardiovascular disease risk; Dense LDL; End-stage renal disease; Glutathione-S-transferase polymorphism; HDL subclasses; Small.