Tumor Necrosis Factor-Alpha Polymorphism at Position -238 in Preeclampsia

Abstract

Background:Preeclampsia is the most common serious disorder during pregnancy and studies show several immune-related processes in its pathophysiology. The role of cytokines and their expression remains controversial in this field. One of the cytokines of interest in recent studies has been TNF-α, which has been shown to have a higher level in maternal plasma of preeclamptic women.Objectives:This study was designed to evaluate the role of TNF-α polymorphism at position -238 in the risk of developing preeclampsia during pregnancy.Patients and Methods:One hundred fifty three preeclamptic cases and 140 healthy pregnant women were retrieved from two major hospitals of Mashhad, Iran. Methods a case-control study were designed. Anyone with a history of inflammatory disease, hypertension, or chronic kidney disease was excluded. DNA was extracted from peripheral blood leukocytes. Both groups were genotyped for the polymorphism of the TNF-α gene at position -238 by the RFLP method with Ava II enzyme. Allele and genotype frequencies were compared using one-way ANOVA and the Fisher’s exact test.Results:There were significant differences between the two groups in TNF-α genotype at position -238 (P < 0.001). In the preeclamptic group, the frequency of the AA genotype was higher (P < 0.001) and the frequency of the GG genotype was lower (P < 0.001). The overall prevalence of the A allele at position -238 was higher in preeclamptic cases (P < 0.001).Conclusion:In this study group, TNF-α -238 polymorphism was shown to be different in preeclamptic and non-preeclamptic pregnant women. The AA genotype and the A allele may carry an increased risk for developing of preeclampsia.

A Case-Control Study Indicates that no Association Exists Between Polymorphisms of IL-33 and IL-1RL1 and Preeclampsia

“…As PE is a polygenetic hereditary disease and previous studies have been indicated that many cytokine genes are associated with susceptibility to it such as VEGF [35,36], NLRP1 [37], IL-1 [15,16], TNF-α [17,18], IFN-γ [19] and so on. Therefore in the present study we investigated whether IL-33 rs3939286 and IL-1RL1 rs13015714 play pivotal roles in the development of PE.…”

“…PE is a complex polygenetic hereditary disease involving both genetic and environmental factors [14] and previous studies have identified many candidate genes associated with susceptibility to it, such as IL-1 [15,16], TNF-α [17,18], IFN-γ [19] and so on. We therefore hypothesize that IL-33 and IL-1RL1 might play critical roles in pathophysiology of PE.…”

Relationship Among Pathophysiology of Gestational Diabetes, Preeclampsia, Vitamin D Level, and Immunomodulation: A Narrative Review

“…Both of these factors lead to vasoconstriction, which can result in the occurrence of hypertension (high blood pressure) involved in preeclampsia (20,21). A study conducted by Farzadnia et al in Mashhad University of Medical Sciences on the genotypes of patients showed that the frequency of AA was significantly higher than GG in patients with preeclampsia (22). Moreover, a study conducted on the mouse cremaster muscle suggested that TNF-α protein resulted in protein leakage from small blood vessels (23).…”

Pro‐inflammatory cytokine single nucleotide polymorphisms in Kawasaki disease

“…TNF‐α polymorphisms at −308 and at −238 are associated with increased incidence of unstable angina and preeclampsia respectively. IL‐6 polymorphism C/G at −174 can predict risk for cardiovascular events …”