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IL-27 variants might be genetic risk factors for preeclampsia: based on genetic polymorphisms, haplotypes and in silico approach

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Abstract

Pre-eclampsia (PE) is a disorder that occurs only during pregnancy. PE is associated with neonate mortality and morbidity. Overexpression of IL-27 and its receptor have been reported frequently in the trophoblast cells of patients with PE. In this study, we aimed to evaluate the relationship between genetic polymorphisms of IL-27 rs153109, and rs17855750 in an Iranian cohort of 170 PE patients and 170 normal pregnant women using the PCR-RFLP method. In the total PE, the frequency of heterozygous and mutant homozygous genotypes of rs153109 was significantly higher, severe, and mild PE groups. The genotypes and alleles frequencies of rs17855750 gene polymorphism were associated with PE susceptibility in total, severe and early-onset sub-group patients. Haplotype analysis of IL-27 rs153109 and rs17855750 polymorphisms revealed that the mutant GG haplotype frequencies significantly increased the risk of preeclampsia in total PE and different sub-group patients, while the wild AT haplotypes were associated with decreased risk of pre-eclampsia in total and sub-group patients. The in-silico analysis showed the transition of allele A to allele G in rs153109 SNP, would lead to create a new binding site and consequently may lead to changes in IL-27 gene expression. We found that rs17855750 A>G polymorphism might be influence the function of IL-27 protein. The data attained in our study propose the incidence of IL-27rs153109 and rs17855750 SNPs might be capable to be utilized as indicators for the genetic susceptibility to PE.

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Abbreviations

PE:

Preeclampsia

IL:

Interleukin

TNF-α:

Tumor necrosis factor alpha

IFN-γ:

Interferon gamma

Th1:

T helper type 1

Th2:

T helper type 2

EBI3:

Epstein-barr virus induced 3

TGF-β1:

Transforming growth factor beta 1

PCR:

Polymerase chain reaction

RFLP:

Restriction fragment length polymorphism

ICAM-1:

Intercellular adhesion molecule 1

VCAM-1:

Vascular cell adhesion molecule 1

FGR:

Fetal growth restriction

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Acknowledgements

This study supported by Grant number 171/94 (Zbmu.1.REC.1396.25) from the Zabol University of Medical Sciences. The authors also would like sincerely thanks of all those who voluntarily have participated in this study.

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Correspondence to Forough Forghani or Mohammad Doroudian.

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Jahantigh, D., Ghazaey Zidanloo, S., Forghani, F. et al. IL-27 variants might be genetic risk factors for preeclampsia: based on genetic polymorphisms, haplotypes and in silico approach. Mol Biol Rep 47, 7929–7940 (2020). https://doi.org/10.1007/s11033-020-05871-z

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