The effects of NLRP3 rs10754558 and rs4612666 polymorphisms on preeclampsia susceptibility, onset, and severity: a case-control study and in silico analysis

Document Type : Original article

Authors

1 Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran

2 Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

3 Department of Obstetrics and Gynecology, Pregnancy Health Research Center, Zahedan University of Medical Sciences, Zahedan, Iran

4 Pregnancy Health Research Center, Zahedan University of Medical Sciences, Zahedan, Iran

5 Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Abstract

Preeclampsia (PE) is one of the serious complications of pregnancy and its exact etiology is unknown. Inflammasomes are multiportion complexes whose relation with PE has been described. Evidence showed the effect of NLRP3 inflammasome in PE pathogenesis. In the current study, we investigated the possible impacts of NLRP3 polymorphisms on PE.  A total of 252 PE and 258 control pregnant women were selected for the study. The PCR-RFLP method was employed to genotype rs10754558 and rs4612666 polymorphisms. The RNAsnp and SpliceAid 2 software were used for in silico analysis. There was no relationship between NLRP3 polymorphisms and PE. In comparison to control women, the NLRP3 rs10754558 could increase the risk of severe PE in codominant and dominant models (OR=1.89, 95% CI=1.19-3.01, P=0.012, OR=1.95, 95% CI=1.24-3.06, P=0.0037, respectively). The findings of the in silico analysis revealed the effects of rs10754558 C to G and rs4612666 C to T substitutions on protein binding sites and rs10754558 C to G substitution on secondary RNA structure. These findings could confirm the finding those studies reported the impacts of these variants on various diseases. In conclusion, the NLRP3 rs10754558 variant was associated with an increased risk of EOPE and severe PE.

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