Candidate gene analysis of femoral neck trabecular and cortical volumetric bone mineral density in older men

Abstract

In contrast to conventional dual-energy X-ray absorptiometry, quantitative computed tomography separately measures trabecular and cortical volumetric bone mineral density (vBMD). Little is known about the genetic variants associated with trabecular and cortical vBMD in humans, although both may be important for determining bone strength and osteoporotic risk. In the current analysis, we tested the hypothesis that there are genetic variants associated with trabecular and cortical vBMD at the femoral neck by genotyping 4608 tagging and potentially functional single-nucleotide polymorphisms (SNPs) in 383 bone metabolism candidate genes in 822 Caucasian men aged 65 years or older from the Osteoporotic Fractures in Men Study (MrOS). Promising SNP associations then were tested for replication in an additional 1155 men from the same study. We identified SNPs in five genes (IFNAR2, NFATC1, SMAD1, HOXA, and KLF10) that were robustly associated with cortical vBMD and SNPs in nine genes (APC, ATF2, BMP3, BMP7, FGF18, FLT1, TGFB3, THRB, and RUNX1) that were robustly associated with trabecular vBMD. There was no overlap between genes associated with cortical vBMD and trabecular vBMD. These findings identify novel genetic variants for cortical and trabecular vBMD and raise the possibility that some genetic loci may be unique for each bone compartment. © 2010 American Society for Bone and Mineral Research

WNT3A gene polymorphisms are associated with bone mineral density variation in postmenopausal mestizo women of an urban Mexican population: findings of a pathway-based high-density single nucleotide screening

“…More recently WNT3A, known to affect osteoblast differentiation (Monroe et al 2012), was found to be associated with BMD in Australian postmenopausal women (Sims et al 2008); a meta-analysis combining five GWAS identified a large linkage disequilibrium (LD) block encompassing LRP4 associated with femoral neck and lumbar spine BMD (Styrkarsdottir et al 2008). It has also been suggested that LRP6 polymorphisms influence BMD (Sims et al 2008;van Meurs et al 2008); however, the results have been conflicting (Mencej-Bedrac et al 2009;Yerges et al 2010). Recently, Estrada et al (2012) performed a metaanalysis including data from 17 genome-wide association studies of European and East Asian ancestry, highlighting the critical role of several genes (WNT16, LRP5, DKK1, LRP4, WNT4.…”

Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in men

“…In contrast, in a relatively large study of men, no significant association was observed between these three genes and volumetric BMD at the femoral neck and lumbar spine (LS) (34) or trabecular and cortical volumetric BMD at the femoral neck. (35) Nevertheless, recently, SNPs located near RANKL, (36) RANK, (37) and OPG (36,38) also have been associated with BMD in genome-wide association studies (GWAS).…”

BMP7 gene polymorphisms are not associated with bone mineral density or osteoporotic fractures in postmenopausal Chinese women

“…Volumetric BMD (vBMD) for both compartments is heritable, with heritability estimates of 17% to 42% for cortical vBMD and 59% to 73% for trabecular vBMD [29][30][31] . In a study aiming to investigate the candidate gene of femoral neck trabecular and cortical vBMD in older men by genotyping 4608 tagging and potentially functional SNPs in 383 bone metabolism candidate genes in 822 Caucasian men aged 65 years or older from the Osteoporotic Fractures in Men Study (MrOS), the results indicated that rs6127983 of BMP7 was robustly associated with trabecular vBMD [32] . Osteoporotic fracture is an outcome of low-trauma to bone of compromised strength, and its incidence is increased by various risk factors.…”