Polymorphisms of the WNT10B gene, bone mineral density, and fractures in postmenopausal women.
Wnt ligands are important regulators of skeletal homeostasis. Wnt10B tends to stimulate the differentiation of common mesenchymal precursors toward the osteoblastic lineage, while inhibiting adipocytic differentiation. Hence, we decided to explore the association of WNT10B allelic variants with bone mineral density and osteoporotic fractures. A set of tag SNPs capturing most common variations of the WNT10B gene was genotyped in 1438 Caucasian postmenopausal women, including 146 with vertebral fractures and 432 with hip fractures. We found no association between single SNPs and spine or hip bone mineral density (BMD). In the multilocus analysis, some haplotypes showed a slight association with spine BMD (P = 0.03), but it was not significant after multiple-test correction. There was no association between genotype and vertebral or hip fractures. Transcripts of WNT10B and other Wnt ligands were detected in human bone samples by real-time PCR. However, there was no relationship between genotype and RNA abundance. Thus, WNT10B is expressed in the bone microenvironment and may be an important regulator of osteoblastogenesis, but we have not found evidence for a robust association of common WNT10B gene allelic variants with either BMD or fractures in postmenopausal women.
Perez-Castrillon
Jose L
JL
Medicina Interna, Hospital U. Rio Hortega, Universidad de Valladolid, Valladolid, Spain.
Olmos
Jose M
JM
Nan
Daniel N
DN
Castillo
Jesus
J
Arozamena
Jana
J
Montero
Antonio
A
Perez-Nuñez
María I
MI
Riancho
Jose A
JA
D000368:Aged; D015519:Bone Density / Q000502:physiology*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D005598:Fractures, Spontaneous / Q000209:etiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006620:Hip Fractures / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011859:Radiography; D016103:Spinal Fractures / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics*
D011518:Proto-Oncogene Proteins; C491119:WNT10B protein, human; D051153:Wnt Proteins