Polymorphisms in Genes Involved in Osteoblast Differentiation and Function Are Associated with Anthropometric Phenotypes in Spanish Women.

Much of the genetic variance associated with osteoporosis is still unknown. Bone mineral density (BMD) is the main predictor of osteoporosis risk, although other anthropometric phenotypes have recently gained importance. The aim of this study was to analyze the association of SNPs in genes involved in osteoblast differentiation and function with BMD, body mass index (BMI), and waist (WC) and hip (HC) circumferences. Four genes that affect osteoblast differentiation and/or function were selected from among the differentially expressed genes in fragility hip fracture (, , , and ), and an association study of four single-nucleotide polymorphisms (SNPs) was conducted in a cohort of 1001 women. Possible allelic imbalance was also studied for SNP rs87939 of the gene. We found significant associations of SNP rs87939 of the gene with LS-sBMD, and of SNP rs1366594 of the gene with BMI, after adjustment for confounding variables. The SNP of the gene also showed a significant trend to association with FN-sBMD ( = 0.009). A possible allelic imbalance was ruled out as no differences for each allele were detected in expression in primary osteoblasts obtained from homozygous women. In conclusion, we demonstrated that two SNPs in the and genes, both implicated in osteoblast differentiation and/or function, are associated with BMI and LS-sBMD, respectively.