title: Estrogen-related genes and postmenopausal osteoporosis risk.
abstract: BACKGROUND
  To date, more than 150 candidate genes related to osteoporosis have been described, but osteoporosis has increasingly been considered a polygenic disease modulated by environmental factors. It is thought that osteoporosis predisposition, pathology, and treatment response depend on the interaction between different genes or between genes and environmental factors.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the relationship between the presence of single nucleotide polymorphisms (SNPs) in the estrogen metabolic pathway and the development of osteoporosis and to determine whether this relationship is monogenic or whether interactions between genes exist.
  
  
  METHODS
  A multicentric study with 1980 postmenopausal Spanish women in five Spanish communities was conducted. The women completed a specific questionnaire that inquired about risk factors for osteoporosis. Data on participants' bone mineral density were obtained with dual-energy X-ray densitometers, and genetic data were obtained from frozen peripheral blood.
  
  
  RESULTS
  The digenic protection combinations indicated involvement of the wild-type genotype (WT) of the 3'UTR marker for the CYP19A1 gene, the IVS4 marker of the same gene, and the BMP15 and FSHR genes. Among patients who carried two or more of the genotypes considered 'risky', the triple combination among markers of the ESR2 and NRIP1 genes with any of the two mutations of the analyzed markers of the BMP15 gene gave a mean T-score value of -2.32±0.91 (p = 0.02).
  
  
  CONCLUSIONS
  Variants of the new candidate genes (NRIP and BMP15) can predispose patients to osteoporosis.
authors.affiliation: Department of Obstetrics and Gynecology, University of Granada, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Mendoza
authors.forename: F
authors.initials: F
authors.lastname: Quereda
authors.forename: J
authors.initials: J
authors.lastname: Presa
authors.forename: A
authors.initials: A
authors.lastname: Salamanca
authors.forename: R
authors.initials: R
authors.lastname: Sánchez-Borrego
authors.forename: F
authors.initials: F
authors.lastname: Vázquez
authors.forename: T
authors.initials: T
authors.lastname: Martínez Astorquiza
mesh_terms: D015502:Absorptiometry, Photon; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000368:Aged; D001141:Aromatase / Q000235:genetics; D015519:Bone Density / Q000235:genetics; D055430:Bone Morphogenetic Protein 15 / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics; D047629:Estrogen Receptor beta / Q000235:genetics; D004967:Estrogens / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D000078723:Nuclear Receptor Interacting Protein 1; D015663:Osteoporosis, Postmenopausal / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011962:Receptors, FSH / Q000235:genetics; D013030:Spain
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C525901:BMP15 protein, human; D055430:Bone Morphogenetic Protein 15; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D011962:Receptors, FSH; D001141:Aromatase; C561410:CYP19A1 protein, human