Interleukin-23 receptor (IL-23R) gene polymorphisms and haplotypes associated with the risk of preeclampsia: evidence from cross-sectional and in silico studies

J Assist Reprod Genet. 2019 Jul;36(7):1523-1536. doi: 10.1007/s10815-019-01479-w. Epub 2019 May 23.

Abstract

Purpose: Pre-eclampsia is a relatively common pregnancy disorder. Serum concentrations of certain pro-inflammatory molecules and cytokines like interleukin-23 may affect the pathogenesis of pre-eclampsia. The interleukin-23 receptor (IL-23R) gene plays an important role in the progression of inflammatory and autoimmune diseases and IL-23 polymorphisms might influence the susceptibility of pre-eclampsia. The aim of the recent study was to establish the association between IL-23R gene polymorphisms and the susceptibility for developing of pre-eclampsia.

Methods: One hundred and fifty-eight pregnant patients with pre-eclampsia and 153 controls were genotyped using RFLP-PCR and AS-PCR. Also, an in silico analysis was performed to predict possible effects of these variations on IL-23R mRNA and protein structures.

Results: The frequency of the AG genotype of rs11209026 is related to a higher risk of pre-eclampsia. The mutant C and A allele in rs10889677 and rs11209026 SNPs, respectively, are correlated with the risk of pre-eclampsia and they are more frequent in severe late onset PE. We found higher frequency of the haplotype CG in patients with pre-eclampsia in comparison to healthy controls, as well as, the CG haplotype frequency significantly increased the risk of PE in severe, early onset, and late onset sub-groups. The results of computational analysis predicted rs11209026 and rs10889677 SNPs as functional variations, which can influence IL-23R mRNA and protein.

Conclusions: The results of present study show positive association between polymorphisms in the IL-23R gene and pre-eclampsia. Therefore, the presence of IL-23R rs11209026, rs10889677 polymorphism might be markers for the genetic susceptibility to pre-eclampsia.

Keywords: Haplotype; In silico; Interleukin-23 receptor (IL-23R); Pre-eclampsia.

MeSH terms

  • Adult
  • Female
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Haplotypes / genetics
  • Humans
  • Male
  • Polymorphism, Single Nucleotide / genetics
  • Pre-Eclampsia / genetics*
  • Pre-Eclampsia / pathology
  • Pregnancy
  • Receptors, Interleukin / genetics*
  • Risk Factors

Substances

  • IL23R protein, human
  • Receptors, Interleukin