Functional polymorphism within NUP210 encoding for nucleoporin GP210 is associated with the risk of endometriosis

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.