Functional Polymorphism Within NUP210 Encoding for Nucleoporin GP210 Is Associated With the Risk of Endometriosis

Fertil Steril. 2019 Aug;112(2):343-352.e1. doi: 10.1016/j.fertnstert.2019.04.011. Epub 2019 Jun 27.

Abstract

Objective: To investigate whether nucleoporin 210 (GP210, encoded by NUP210 gene) is involved in endometriosis.

Design: Immunohistofluorescence analysis for assessing whether GP210 is expressed in endometrial tissues from patients and controls; genotyping and case-control study for assessing the association between rs354476 within NUP210 and risk of endometriosis; in vitro luciferase assay for assessing the functional activity of rs354476.

Setting: University.

Patient(s): Histologically diagnosed cases (n = 175) of endometriosis: minimal or mild (stage I-II) in 48 cases (28%), moderate (stage III) in 69 cases (39%), and severe (stage IV) in 58 cases (33%). Controls (n = 557) were female blood donors collected at Meyer Hospital of Florence.

Intervention(s): None.

Main outcome measure(s): GP210 tissue expression; genotype distribution and risk of endometriosis; in vitro gene expression measurements.

Result(s): GP210 had positive nuclear immunohistofluorescence staining in endometrial glandular epithelium. Carriers of the variant allele were associated with increased risks: C/T, odds ratio (OR) 1.83, 95% confidence interval (CI) 1.04-3.21; T/T, OR 2.55, 95% CI 1.36-4.80. In vitro, luciferase assay showed that rs354476 is a bona fide target for hsa-miR-125b-5p.

Conclusion(s): Nucleoporin GP210 is involved in endometriosis. Rs354476 polymorphism affects the regulation of NUP210 gene expression by altering the binding with hsa-miR-125b-5p, a microRNA already known as playing an important role for endometriosis. This provides the rationale for the observed increased risk of endometriosis in carriers of the variant allele.

Keywords: Endometrium; NUP210; glycoprotein-210; miRNA binding sites; polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Endometriosis / genetics*
  • Endometriosis / pathology
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Nuclear Pore Complex Proteins / genetics*
  • Polymorphism, Single Nucleotide*
  • Severity of Illness Index
  • Uterine Diseases / genetics*
  • Uterine Diseases / pathology
  • Young Adult

Substances

  • NUP210 protein, human
  • Nuclear Pore Complex Proteins