Preliminary molecular genetic analysis of the Receptor Interacting Protein 140 (RIP140) in women affected by endometriosis

  • Virginia Caballero
  • Rocío Ruiz
  • José Antonio Sainz
  • Marina Cruz
  • Miguel Angel López-Nevot
  • José Jorge Galán
  • Luis Miguel Real
  • Francisco de Castro
  • Vicente López-Villaverde
  • Agustín Ruiz
Open Access
Research

Abstract

Background

Endometriosis is a complex disease affecting 10–15% of women at reproductive age. Very few genes are known to be altered in this pathology. RIP140 protein is an important cofactor of oestrogen receptor and many other nuclear receptors. Targeting disruption experiments of nrip1 gene in mice have demonstrated that nuclear receptor interacting protein 1 gene (nrip1), the gene encoding for rip140 protein, is essential for female fertility. Specifically, mice null for nrip1 gene are viable, but females are infertile because of complete failure of mature follicles to release oocytes at ovulation stage. The ovarian phenotype observed in mice devoid of rip140 closely resembles the luteinized unruptured follicle (LUF) syndrome that is observed in a high proportion of women affected of endometriosis or idiopathic infertility. Here we present a preliminary work that analyses the role of NRIP1 gene in humans.

Methods

We have sequenced the complete coding region of NRIP1 gene in 20 unrelated patients affected by endometriosis. We have performed genetic association studies by using the DNA variants identified during the sequencing process.

Results

We identified six DNA variants within the coding sequence of NRIP1 gene, and five of them generated amino acid changes in the protein. We observed that three of twenty sequenced patients have specific combinations of amino-acid variants within the RIP140 protein that are poorly represented in the control population (p = 0.006). Moreover, we found that Arg448Gly, a common polymorphism located within NRIP1 gene, is associated with endometriosis in a case-control study (59 cases and 141 controls, pallele positivity test = 0.027).

Conclusion

Our results suggest that NRIP1 gene variants, separately or in combinations, might act as predisposing factors for human endometriosis.

Notes

Acknowledgements

We are deeply grateful to patients and controls for participation in this study. Funded by the Ministerio de Ciencia y Tecnología (MCYT, Spain, grant numbers FIT-010000-2003-36, FIT-010000-2003-89, FIT-010000-2003-70, PTQ2002-0206) and Organón Española S.A. (BCN, Spain).

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Copyright information

© Caballero et al; licensee BioMed Central Ltd. 2005

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Authors and Affiliations

  • Virginia Caballero
    • 2
  • Rocío Ruiz
    • 1
  • José Antonio Sainz
    • 2
  • Marina Cruz
    • 2
  • Miguel Angel López-Nevot
    • 3
  • José Jorge Galán
    • 1
  • Luis Miguel Real
    • 1
  • Francisco de Castro
    • 4
  • Vicente López-Villaverde
    • 2
  • Agustín Ruiz
    • 1
  1. 1.Department of Structural GenomicsneoCodexSevilleSpain
  2. 2.Unidad de Reproducción. Servicio de Obstetricia y GinecologíaHospital de ValmeSevilleSpain
  3. 3.Servicio de Análisis ClínicosHospital Universitario Virgen de las NievesGranadaSpain
  4. 4.Unidad de Reproducción Humana AsistidaHospital Universitario Príncipe de AsturiasMadridSpain

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