title: Relationship of sclerostin and secreted frizzled protein polymorphisms with bone mineral density: an association study with replication in postmenopausal women.
abstract: OBJECTIVE
  Secreted frizzled-related protein and sclerostin, encoded by FRZB and SOST genes, respectively, are extracellular Wnt inhibitors that tend to decrease bone formation. The purpose of this study was to explore the association of the sets of polymorphisms capturing common variations of these genes with bone mineral density (BMD).
  
  
  METHODS
  Twelve polymorphic loci of the FRZB gene and 7 of the SOST gene were genotyped in postmenopausal women from two Spanish regions (Cantabria, n = 1043, and Valencia, n = 342). The polymorphisms included tagging single nucleotide polymorphisms and single nucleotide polymorphisms with possible functional consequences assessed in silico.
  
  
  RESULTS
  The rs4666865 polymorphism of the FRZB gene was associated with spine BMD in the Cantabria cohort in the single-locus (P = 0.008) and the haplotypic analysis. However, the results were not replicated in the Valencia cohort. Several polymorphisms at the 5' region of the SOST gene and, particularly, rs851056 were associated with BMD in women from both cohorts (P = 0.002 in Cantabria and P = 0.005 in Valencia). When the results of both cohorts were combined, the mean (SD) BMD difference across rs851056 genotypes was 47 (0.31) mg/cm(2) (P < 0.001). No differences in FRZB and SOST expression in femoral trabecular bone tissue were detected across genotypes.
  
  
  CONCLUSIONS
  Polymorphisms in the 5' region of SOST gene are associated with BMD in postmenopausal women. They may contribute to explain, in part, the hereditary influence on bone mass.
authors: Department of Internal Medicine, Hospital UM Valdecilla, University of Cantabria, IFIMAV, RETICEF, Valencia, Spain.
authors: Carmen
authors: C
authors: Valero
authors: María T
authors: MT
authors: Zarrabeitia
authors: José L
authors: JL
authors: Hernández
authors: Begoña
authors: B
authors: Pineda
authors: Antonio
authors: A
authors: Cano
authors: Miguel A
authors: MA
authors: García-Pérez
authors: José A
authors: JA
authors: Riancho
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D015519:Bone Density / Q000235:genetics*; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D001842:Bone and Bones / Q000378:metabolism; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000235:genetics; D013030:Spain; D000099274:Frizzled-Related Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D000099274:Frizzled-Related Proteins; C422903:SOST protein, human