Promoter 2 -1025 T/C polymorphism in the RUNX2 gene is associated with femoral neck bmd in Spanish postmenopausal women.
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.
Bustamante
Mariona
M
Department of Genetics, University of Barcelona, Av Diagonal, 645, E-08028, Barcelona, Spain.
Nogués
Xavier
X
Agueda
Lídia
L
Jurado
Susana
S
Wesselius
Anke
A
Cáceres
Enrique
E
Carreras
Ramon
R
Ciria
Manel
M
Mellibovsky
Leonardo
L
Balcells
Susana
S
Díez-Pérez
Adolfo
A
Grinberg
Daniel
D
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
D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human