Anti-TNFRSF11A (aa 31-130) polyclonal antibody

RANK (receptor activator of nuclear factor-kappa B), encoded by TNFRSF11A, is a key protein in osteoclastogenesis TNFRSF11A mutations cause Paget's disease of bone (PDB)-like diseases (ie, familial expansile osteolysis, expansile skeletal hyperphosphatasia, and early-onset PDB) and an osteoclast-poor form of osteopetrosis However, no TNFRSF11A mutations have been found in classic PDB, neither in familial nor in isolated cases To investigate the possible relationship between TNFRSF11A polymorphisms and sporadic PDB, we conducted an association study including 32 single-nucleotide polymorphisms (SNPs) in 196 Belgian sporadic PDB patients and 212 control individuals Thirteen SNPs and 3 multimarker tests (MMTs) turned out to have a p value of between 036 and 317 x 10(-4), with the major effect coming from females Moreover, 6 SNPs and 1 MMT withstood the Bonferroni correction (p < 002) Replication studies were performed for 2 nonsynonymous SNPs (rs35211496 and rs1805034) in a Dutch and a British cohort Interestingly, both SNPs resulted in p values ranging from 013 to 838 x 10(-5) in both populations Meta-analysis over three populations resulted in p = 002 for rs35211496 and p = 1 27 x 10(-8) for rs1805034, again mainly coming from the female subgroups In an attempt to identify the underlying causative SNP, we performed functional studies for the coding SNPs as well as resequencing efforts of a 31-kb region harboring a risk haplotype within the Belgian females However, neither approach resulted in significant evidence for the causality of any of the tested genetic variants Therefore, further studies are needed to identify the real cause of the increased risk to develop PDB shown to be present within TNFRSF11A (C) 2010 American Society for Bone and Mineral Research

The regulation of bone remodeling is controlled by the cellular interactions between osteoblasts and osteoclasts in which the OPG/RANKL/RANK pathway plays a paramount role. The aim of this study was to assess whether exists differences between polymorphisms of the TNFSF11, TNFRSF11A and TNFRSF11B genes in the OPG/RANKL/RANK pathway and different populations. In the present study, we genotyped 41 single-nucleotide polymorphisms (SNPs) in the TNFSF11, TNFRSF11A, and TNFRSF11B genes in the Mongols and Han populations of Northwest China. Mongols compared with five other populations: the Chinese Han in Beijing, China (CHB), the Japanese in Tokyo, Japan (JPT), a northern and western European population (CEU), the Yoruba in Ibadan, Nigeria (YRI) and Northwest Han Chinese using chi-squared tests and haplotype analysis. We determined that Mongols differed from CHB, CEU, JPT, YRI and Northwest Han Chinese in 1, 19, 1, 17 and 1 selected SNP genotypes after Bonferroni correction (P < 0.05/40(star)6), respectively. The rs3826617 in TNFRSF11A gene was significantly different compared with three ethnic populations (CHB, JPT and YRI). The rs8092023 in the TNFRSF11A gene just showed a significant difference compared with that in Northwest Han Chinese. Differences of polymorphisms of TNFSF11 and TNFRSF11B genes just were found in the CEU and YRI compared with that in Mongols. Haplotype analysis also demonstrated differences between the Mongols and the other five populations. Our results illustrate for the first time the differences of polymorphisms of the TNFSF11, TNFRSF11A, and TNFRSF11B genes between Mongols and five other populations and may provide available information regarding genetic polymorphisms in the OPG/RANKL/RANK pathway of different populations and osteopathy-association studies.