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

The Rs354476 polymorphism affects the regulation of NUP210 by altering the binding with hsa-miR-125b- 5p; this provides the rationale for the observed increased risk of endometriosis in carriers of the variant allele

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Volume 112, Issue 2, Pages 343–352.e1

Authors:

Monica Cipollini, Ph.D., Stefano Luisi, M.D., Ph.D., Paola Piomboni, Ph.D., Alice Luddi, Ph.D., Debora Landi, Ph.D., Ombretta Melaiu, Ph.D., Gisella Figlioli, Ph.D., Sonia Garritano, Ph.D., Valentina Cappelli, M.D., Paola Viganò, Ph.D., Federica Gemignani, Ph.D., Felice Petraglia, M.D., Stefano Landi, Ph.D.

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 NUP210gene 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.


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Fertility and Sterility

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1 Comments

Tom Meier about 1 month ago

Some of the data are inconclusive:


This is an interesting study on a SNP in the nuclear pore complex protein (NUP) gene NUP210 that impacts binding of hsa-miR-125b-5p. As indicated in the introduction, we showed that only certain NUPs are present in nucleolar channel systems of midluteal endometrial epithelial cell nuclei, but all NUPs are housekeeping proteins and stain the nuclear pore complexes of all cells, epithelial, stromal, etc. (e.g., references 37 and 41). Unfortunately, there is no nuclear pore staining detectable in any of the panels of Figure 1. There is only staining visible in the cytoplasm, but NUP210 is a nuclear pore complex protein and should thus yield a distinct punctate rim staining pattern outlining nuclei or a punctate pattern when focusing on the surface of nuclei, as documented in countless other publications. Consequently, before any conclusions can be drawn, the antibodies to NUP210 need to be verified and show a clear nuclear rim staining in control endometrium (we tested many NUP antibodies and some just do not work on endometrial tissue).