Combination Effect of GSTM1, GSTT1 and GSTP1 Polymorphisms and Risk of Systemic Lupus Erythematosus

Abstract

Background: Progression of systemic lupus erythematosus (SLE) could be due to oxidative stress especially through reactive oxygen species (ROS). Detoxification of ROS is largely performed by Glutathione S-transferases (GSTs), therefore polymorphisms of GSTM1, GSTT1 and GSTP1 genes which decrease enzymes activity could affect SLE susceptibility. The aim of this study was to determine the effects of GSTM1 (deletion), GSTT1 (deletion) and GSTP1 (Ile105Val) polymorphisms on SLE susceptibility.

Methods: Genomic DNA was extracted from blood samples of 163 SLE patients and 180 age, sex and ethnically matched controls. GSTs genotypes were determined by polymerase chain reaction (PCR)-multiplex procedure or pol-ymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.

Results: GSTT1 null genotype frequency was higher in SLE patients than controls. NO association observed between GSTM1 null genotype or GSTP1 Ile105Val polymorphism with SLE. Nevertheless combination of GSTT1 null/ GSTM1 null genotypes showed 2.8-fold increase in risk of SLE. Moreover the combination of GSTT1 null/ GSTM1 null/GSTP1 Ile/Val and Val/Val genotypes increased the SLE risk about 8 fold.

Conclusion: Present data suggest that GSTT1 null/ GSTM1 null/GSTP1 Ile/Val and Val/Val genotypes might large-ly contribute to the pathogenesis of SLE.