The role of TNF-α and TLR4 polymorphisms in the placenta of pregnant women complicated by preeclampsia and in silico analysis

• Published in: International journal of biological macromolecules Vol. 134; pp. 1205 - 1215
• Main Authors: Mohammadpour-Gharehbagh, Abbas, Jahantigh, Danial, Eskandari, Moein, Eskandari, Fatemeh, Rezaei, Mahnaz, Zeynali-Moghaddam, Shima, Teimoori, Batool, Salimi, Saeedeh
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2019
• Subjects: Adult; Alleles; Binding Sites; Computational Biology - methods; Cytokines - metabolism; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Inflammation Mediators - metabolism; Models, Molecular; Nucleic Acid Conformation; Odds Ratio; Placenta; Placenta - metabolism; Polymorphism; Polymorphism, Single Nucleotide; Pre-Eclampsia - genetics; Pre-Eclampsia - metabolism; Pre-Eclampsia - physiopathology; Preeclampsia; Pregnancy; Protein Binding; Structure-Activity Relationship; TLR4; TNF-α; Toll-Like Receptor 4 - chemistry; Toll-Like Receptor 4 - genetics; Tumor Necrosis Factor-alpha - chemistry; Tumor Necrosis Factor-alpha - genetics; Young Adult; Placenta; TNF-α; TLR4; Preeclampsia; Polymorphism
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2019.05.040

Evidence showed that, pro inflammatory cytokines and mediators of innate immune responses may involve in the pathogenesis of preeclampsia (PE). Therefore, the present investigation aimed to examine the possible effects of placental TNF-α and TLR4 polymorphisms on PE susceptibility. The placental tissues were collected after delivery from 111 PE and 115 healthy pregnant women. The TNF-α-308G/A (rs1800629), TNF-α-238G/A (rs361525), TLR4 Asp299Gly (rs4986790) and TLR4 Thr399Ile (rs4986791) polymorphisms were genotyped using PCR-RFLP method. Moreover, in-silico analysis was performed to evaluate the potential functions of these polymorphisms. The TNF-α −308 GA genotype was associated with a decreased PE risk. The frequency of TNF-α −238G/A genotypes did not differ between two groups, however, the frequency of TNF-α −238A allele was significantly higher in controls. No relationship between TLR4 Thr399Ile and Asp299Gly polymorphisms and PE was found. In-silico analysis predicted that −308G to A substitution in the TNF-α promoter might lead to different allelic expressions. In addition, TLR4 Asp299Gly polymorphism would result in a major change in the mRNA and protein functions. Our study for the first time presented evidence on the association of the placental TNF-α −308GA genotype and TNF-α −238A allele with decreased risk of PE in an Iranian population. •The placenta tissues of 111 PE pregnant women and 115 normotensive pregnant women were collected after delivery.•The frequency of TNF-308-α GA genotype was significantly higher in controls compared to that in PE women and this genotype could be a protective factor for PE susceptibility.•No significant association was observed between Thr399Ile and Asp299Gly polymorphisms of TLR4 gene and PE susceptibility.