Glutathione‐S‐transferase M1 polymorphism and pro‐inflammatory cytokines tumour necrosis factor‐α and interleukin‐1β 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‐α, IL‐1β, 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‐α was significantly higher in preeclampsia compared to healthy pregnant women (P = 0.006). Expression of IL‐1β 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‐α and IL‐1β was observed (Spearman's ρ = 0.312, P = 0.028) and between IL‐1β and IL‐6, in preeclampsia group (Spearman's ρ = 0.296, P = 0.037). IL‐1β 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‐α and IL‐1β.

Association of polymorphisms in TNF‐α, IL‐1β, GSTM and GSTT genes with apical periodontitis: is there a link with herpesviral infection?

“…In accordance with the finding of the present study, Concolino et al (2007) and Camargo Ortega et al (2014) have reported that subjects with null and double‐null GSTM1 and GSTT1 genotypes have a higher risk of developing aggressive and chronic periodontitis. This study is also in agreement with previous reports on GST deletion polymorphisms as significant modulators of temporomandibular disorders (Milosevic et al 2015), pre‐eclampsia (Sljivancanin Jakovljevic et al 2019) and atherogenesis (Grubisa et al 2018) risk in Serbian populations.…”

Lack of association between glutathione S‐transferase M1 and T1 gene polymorphisms and susceptibility to preeclampsia: An updated systematic review and meta‐analysis

“…Two studies were excluded due to repeated data, 35,36 eventually leaving 10 articles with sufficient data about genotype frequencies of both GST M1 and GST T1 deletion polymorphism in women with preeclampsia and healthy pregnant controls, which were included in the final review. [20][21][22][23][24][37][38][39][40][41] A detailed description of the characteristics extracted from the included studies is shown in Table 1. Out of 2831 participants included in this systematic review, 1259 were preeclampsia cases and 1572 were controls.…”

“…Five out of ten researches investigated frequencies of combined GST M1 and GST T1 genotypes. [20][21][22][23][24] Methodological rigor and quality were assessed using the STREGA recommendations. The total quality scores of the included studies ranged from 9 to 18 in the STREGA checklist.…”

“…19 Several studies have also examined GST T1 and GST M1 deletion polymorphism in PE, with very conflicting results. [20][21][22][23][24] A study on Mexican Mestizo women showed susceptibility to PE among carriers of GST T1 null genotype. 20 Oppositely, a study on Chinese Han population of woman described a protective effect of GST T1 deletion.…”

“…21 GST M1 homozygous deletion was related to increased preeclampsia risk in Serbian and Bangladesh women. 22,23 After the publication of the first meta-analysis on the association between GSTM1 and GSTT1 gene polymorphisms and PE risk, in 2011, 24 several investigations on this topic on different populations were performed. Rather inconsistent results on the link between GST M1 and GST T1 polymorphisms and PE susceptibility were obtained, implying the necessity of an updated meta-analysis.…”