Glutathione-S-transferase M1 polymorphism and pro-inflammatory cytokines tumour necrosis factor-alpha and interleukin-1 beta are associated with preeclampsia in Serbian women

Abstract

Problem Preeclampsia has a multifactorial origin with genetic, immunological, and environmental factors described as main contributors to its onset. This study aimed to investigate glutathione-S-transferase M1 (GSTM1) and glutathione-S-transferase T1 (GSTT1) gene polymorphisms, the expression of pro-inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6), and the potential relationship between GST polymorphisms and cytokine expression levels in preeclampsia and uncomplicated pregnancy. Method of Study This prospective case-control study included 50 women with preeclampsia and 50 healthy pregnant women. DNA and RNA were extracted from women leukocytes. Deletion polymorphisms were analyzed by PCR, while cytokine mRNA expression was analyzed by real-time PCR. Results GSTM1 null genotype with present GSTT1 increased the risk for preeclampsia development. Deletion of GSTT1 without deletion of GSTM1 increased the risk for early preeclampsia. Relative mRNA expression of TNF-alpha was significantly higher in preeclampsia compared to healthy pregnant women (P = 0.006). Expression of IL-1 beta was significantly higher in severe and late preeclampsia compared to the control group (P = 0.005, P = 0.007, respectively). A significant positive correlation between TNF-alpha and IL-1 beta was observed (Spearman's rho = 0.312, P = 0.028) and between IL-1 beta and IL-6, in preeclampsia group (Spearman's rho = 0.296, P = 0.037). IL-1 beta was significantly increased in patients with GSTT1 null genotype (P = 0.015) while IL-6 was increased in patients with GSTM1 null genotype (P = 0.015). Conclusions GSTM1 null genotype represents a risk factor for preeclampsia development, while GSTT1 null genotype favors early preeclampsia. Preeclampsia is also associated with increased expression of pro-inflammatory cytokines, predominantly TNF-alpha and IL-1 beta.