title: Promoter 2 -1025 T/C polymorphism in the RUNX2 gene is associated with femoral neck bmd in Spanish postmenopausal women.
abstract: Stimulation of bone formation is a key therapeutic target in osteoporosis. Runx2 is a runt domain transcription factor essential to osteoblast differentiation, bone remodeling, and fracture healing. Runx2 knockout mice exhibit a complete lack of ossification, while overexpression of this gene in transgenic mice results in an osteoporotic phenotype. Thus, RUNX2 is a good candidate for the genetic determination of osteoporosis. In this association study, the effects of the -330 G/T polymorphism in promoter 1 and the -1025 T/C polymorphism (rs7771980) in promoter 2 of RUNX2 were tested in relation to lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) in a cohort of 821 Spanish postmenopausal women. The minor allele frequencies for the two polymorphisms were 0.15 and 0.07, respectively. The two polymorphisms, located more than 90 kb apart, were not in linkage disequilibrium (D' = 0.27, r (2) = 0.028). In an ANCOVA test adjusting by weight, height, age, and years since menopause, the -330 G/T polymorphism was not associated with any of the phenotypes analyzed, while we found the -1025 T/C polymorphism to be associated with FN BMD (p = 0.001). In particular, individuals carrying the TC genotype had higher mean adjusted FN BMD values than those bearing the TT genotype. Our results highlight the importance of this RUNX2 promoter 2 polymorphism in FN BMD determination.
authors: Department of Genetics, University of Barcelona, Av Diagonal, 645, E-08028, Barcelona, Spain.
authors: Mariona
authors: M
authors: Bustamante
authors: Xavier
authors: X
authors: Nogués
authors: Lídia
authors: L
authors: Agueda
authors: Susana
authors: S
authors: Jurado
authors: Anke
authors: A
authors: Wesselius
authors: Enrique
authors: E
authors: Cáceres
authors: Ramon
authors: R
authors: Carreras
authors: Manel
authors: M
authors: Ciria
authors: Leonardo
authors: L
authors: Mellibovsky
authors: Susana
authors: S
authors: Balcells
authors: Adolfo
authors: A
authors: Díez-Pérez
authors: Daniel
authors: D
authors: Grinberg
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D000483:Alleles; D015519:Bone Density / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D005260:Female; D005272:Femur Neck / Q000473:pathology*; D005787:Gene Frequency; D006801:Humans; D008159:Lumbar Vertebrae / Q000502:physiology; D008875:Middle Aged; D010024:Osteoporosis / Q000235:genetics / Q000473:pathology; D011110:Polymorphism, Genetic; D017698:Postmenopause; D011401:Promoter Regions, Genetic; D013030:Spain
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human