title: Preliminary molecular genetic analysis of the Receptor Interacting Protein 140 (RIP140) in women affected by endometriosis.
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).
  
  
  CONCLUSIONS
  Our results suggest that NRIP1 gene variants, separately or in combinations, might act as predisposing factors for human endometriosis.
authors.affiliation: Servicio de Obstetricia y Ginecología, Hospital de Valme, Ctra. Cádiz, s/n 41014 Seville, Spain. virginia.caballero.sspa@juntadeandalucia.es
authors.forename: Virginia
authors.initials: V
authors.lastname: Caballero
authors.forename: Rocío
authors.initials: R
authors.lastname: Ruiz
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Sainz
authors.forename: Marina
authors.initials: M
authors.lastname: Cruz
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: López-Nevot
authors.forename: José Jorge
authors.initials: JJ
authors.lastname: Galán
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Real
authors.forename: Francisco
authors.initials: F
authors.lastname: de Castro
authors.forename: Vicente
authors.initials: V
authors.lastname: López-Villaverde
authors.forename: Agustín
authors.initials: A
authors.lastname: Ruiz