Association of the 163A/G and 1181G/C Osteoprotegerin Polymorphism with Bone Mineral Density

Abstract

The aim of the study was to investigate the distribution of 163 A/G osteoprotegerin gene promoter and 1181 G/C osteoprotegerin exon 1 polymorphisms in a group of women with different hormonal status and to analyze their relationship with BMD. Osteoprotegerin polymorphisms and BMD were analyzed in 332 women (69 premenopausal and 263 postmenopausal). BMD was quantified at the lumbar spine (L 2-4), femoral neck, and total hip. Genotyping for the presence of different polymorphisms was performed using the Custom Taqman ((R)) SNP Genotyping assays. There were not significant differences in BMD according to 163 A/G genotype. However, significant differences in lumbar spine BMD were found according to 1181 G/C alleles. Thus, women with CC genotype had significant higher BMD at the lumbar spine than those with GC or GG genotype. No differences were found in femoral neck and total hip BMD. In age-adjusted models, the 1181 G/C OPG polymorphism explained 2.2% of BMD variance at the spine, 0.3% at the femoral neck, and 0.9% at the total hip in the whole group. In the subgroup of premenopausal women, the polymorphism was strongly related to spine BMD, and explained 11.5% of the variance, whereas body weight explained 7.9%. The 1181 G/C polymorphism was associated with lumbar spine BMD in Spanish women. Premenopausal women with the CC genotype had a higher BMD.

The combinations of polymorphisms in vitamin D receptor, osteoprotegerin and tumour necrosis factor superfamily member 11 genes are associated with bone mineral density

“…In K3N(OPG), women with GG genotype had significantly lower BMDls than those with GC or CC genotype, which is in accordance with several earlier studies (Langdahl et al 2002, Arko et al 2005, Choi et al 2005 Kim et al 2007, García-Unzueta et al 2008. Our previous study on the TNFSF11 gene promoter SNPs, involving 404 post-menopausal women, showed association with BMD-ls for K290COT, K643COT and K693GOC (Mencej et al 2008).…”

“…In a prospective multicentre large-scale association study involving 26 242 participants, only the Cdx2 polymorphism in the VDR gene was found to be associated with the risk of vertebral fractures (Uitterlinden et al 2006). In the OPG gene, several association studies have consistently shown an association of the K3N polymorphism with the osteoporotic phenotype (Langdahl et al 2002, Arko et al 2005, Choi et al 2005, Kim et al 2007, García-Unzueta et al 2008. However, some studies revealed a non-significant association of K3N with the osteoporotic phenotype (Wynne et al 2002, Ueland et al 2007.…”

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

“…(36) Previous candidate gene association studies also have reported an association between rs2073618 and LS BMD a . (15,25,26,29) This association has been confirmed in a meta-analysis study by Lee and colleagues as well. (44) In our study, the minor alleles of rs2073618 and rs9594738 were associated with lower LS BMD a .…”

Allelic variations of RANKL/OPG signaling system are related to bone mineral density and in vivo gene expression

“…We found an association between the rs3102735 polymorphism and BMD, but did not find any effect on the fracture risk; however, the present study was underpowered to show small effects. Other authors (16,17,35) have reported no effect of this genetic variation on BMD. There are several possible explanations for these discrepancies.…”

“…TNFRSF11B knockout mice developed severe OP (10,11), while overexpression of TNFRSF11B in transgenic mice resulted in osteopetrosis (6). Polymorphisms of the TNFRSF11B gene may contribute to the genetic regulation of bone mass as suggested by several recent publications, but the results are somewhat contradictory (12)(13)(14)(15)(16). The ambiguous results include the frequently investigated rs3102735 single nucleotide polymorphism (SNP) effects on BMD and fracture risk (14,17).…”