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

Journal of Experimental & Clinical Assisted Reproduction volume 2, Article number: 11 (2005) Cite this article

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.

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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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Authors and Affiliations

  1. Department of Structural Genomics, neoCodex, Averroes N°8. Edf. Acrópolis 110-1, 41020, Seville, Spain

    Rocío Ruiz, José Jorge Galán, Luis Miguel Real & Agustín Ruiz

  2. Unidad de Reproducción. Servicio de Obstetricia y Ginecología, Hospital de Valme, Ctra. Cádiz, s/n, 41014, Seville, Spain

    Virginia Caballero, José Antonio Sainz, Marina Cruz & Vicente López-Villaverde

  3. Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Avda. Fuerzas Armadas, 2, 18014, Granada, Spain

    Miguel Angel López-Nevot

  4. Unidad de Reproducción Humana Asistida, Hospital Universitario Príncipe de Asturias, Ctra. Alcalá-Meco s/n, 28805, Madrid, Spain

    Francisco de Castro

Authors
  1. Virginia Caballero
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  2. Rocío Ruiz
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  3. José Antonio Sainz
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  4. Marina Cruz
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  7. Luis Miguel Real
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  10. Agustín Ruiz
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Corresponding author

Correspondence to Agustín Ruiz.

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Competing interests

The author(s) declare that they have not competing interests.

Authors' contributions

VC, JAS, MC, MAL, FC and VL carried out the recruitment and classification of patients and controls and the biological samples management. RR and JJG carried out the molecular genetic studies and participate in the analysis and interpretation of data. LMR and AR carried out the design of the study, performed the statistical analyses and the interpretation of data.

All authors have been involved in drafting the article or revising it critically for important intellectual content and have given final approval of the version to be published.

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

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Caballero, V., Ruiz, R., Sainz, J.A. et al. Preliminary molecular genetic analysis of the Receptor Interacting Protein 140 (RIP140) in women affected by endometriosis . J Exp Clin Assist Reprod 2, 11 (2005). https://doi.org/10.1186/1743-1050-2-11

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Journal of Experimental & Clinical Assisted Reproduction

ISSN: 1743-1050