<i>SOST</i>
            Polymorphisms and Response to Alendronate Treatment in Postmenopausal Chinese Women With Osteoporosis

Zhou, Peiran; Xu, Xiaowei; Zhang, Zhenlin; Liao, Er-Yuan; Chen, Decai; Liu, Jian; Wang, Wen; Jiang, Yan; Wang, Ou; Xia, Weibo; Xing, Xiaoping; Xu, Li; Li, Mei

doi:10.2217/pgs.15.76

Cited by 16 publications

(11 citation statements)

References 37 publications

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“…Recent advances in genome-wide methylation methods have provided the means to identify differentially methylated genes, methylation signatures which have the potential to be used as biomarkers. SOST is an important player in the pathogenesis of osteoporosis [42, 43]; the finding that its expression is associated with DNA methylation could make it a useful biomarker of diagnosis of osteoporosis.…”

Section: Discussionmentioning

confidence: 99%

Expression of Sclerostin in Osteoporotic Fracture Patients Is Associated with DNA Methylation in the CpG Island of the SOST Gene

Cao

Wang

et al. 2019

International Journal of Genomics

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Purpose SOST gene is one of the key factors in regulating bone absorption. Although there are reports showing diverse transcription factors, epigenetic modification could be responsible for regulating SOST gene expression. There is still little exploration on promoter methylation status of SOST gene in osteoporotic bone tissues. The aim of this study is to investigate the involvement of CpG methylation in regulation of SOST expression in patients with primary osteoporosis. Methods The diagnosis of osteoporosis was established on the basis of dual energy X-ray absorptiometry to measure BMD. All femoral bone tissues were separated in surgeries. After extracting total RNA and protein, we checked the relative expression levels of SOST by quantitative real-time PCR and western blot. Also, immunohistochemical staining was performed to observe the expression of SOST protein in the bone samples. The genomic DNA of non-OPF (non-osteoporotic fracture bone tissues) and OPF (osteoporotic fracture bone tissues) were treated by bisulfite modification, and methylation status of CpG sites in the CpG island of SOST gene promoter was determined by DNA sequencing. Results SOST gene expression in the non-OPF group was lower than that in OPF group. Bisulfite sequencing result showed that SOST gene promoter was slightly demethylated in the OPF group, as compared with non-OPF group. Conclusion Our study demonstrated that DNA methylation influenced the transcriptional expression of SOST gene, which probably may play an important role in the pathogenesis of primary osteoporosis.

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Section: Discussionmentioning

confidence: 99%

Expression of Sclerostin in Osteoporotic Fracture Patients Is Associated with DNA Methylation in the CpG Island of the SOST Gene

Cao

Wang

et al. 2019

International Journal of Genomics

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“…Since OPG is a decoy receptor for RANKL, it results in the inhibition of bone resorption. In line with this, several investigators have proposed that some polymorphisms of genes related to the Wnt pathway, such as the Wnt co-receptor LRP5, the intracellular signal transducer GSK, or the ligand inhibitor sclerostin, are associated with the response to bisphosphonates and raloxifene [43][44][45][46] . However, negative results were found in some studies [47 ] and a complete independent replication of those findings is still pending.…”

Section: Genetic Factors Influencing Drug Responsementioning

confidence: 93%

Genetic and acquired factors influencing the effectiveness and toxicity of drug therapy in osteoporosis

López-Delgado¹,

Riancho‐Zarrabeitia²,

Riancho³

2016

Expert Opinion on Drug Metabolism & Toxicology

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“…Between the two GEFOS studies, 7 same significant gene pairs were detected on FN-BMD, as were 10 same gene pairs for LS-BMD (Supplementary Table 4). Among these gene pairs, SOST-SP7 and AXIN1-LRP5 were simultaneously significantly associated with FN-BMD and LS-BMD, whose genes were already reported to play important roles in regulating BMDs on more than one skeletal sites in silico and/or in vivo , and in clinical studies [32, 37–39]. The significant PPI pairs and involved genes from GEFOS2 and GEFOS-seq studies are detailed in Supplementary Tables 5 and 6, respectively.…”

Section: Resultsmentioning

confidence: 96%

“…Since the results derived from GWASs can originate from different cells and tissues in humans, it is reasonable to partially validate the association of the identified genes with BMD using the transcriptomics data from various cells/tissues related to bone metabolism. These gene expression data are derived from multiple bone-related cell sources (e.g., peripheral blood monocytes [32], osteocytes [33], and circulating B cells [34]) of females with discordant BMD. The basic characteristics of the subjects are shown in Supplementary Table 1.…”

Section: Methodsmentioning

confidence: 99%

Gene-based GWAS analysis for consecutive studies of GEFOS

Zhu

Zhang

et al. 2018

Osteoporos Int

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Purpose Single-nucleotide polymorphism (SNP)-based genome-wide association studies (GWASs) have already identified about 100 loci associated with bone mineral density (BMD), but these loci only explain a small proportion of heritability to osteoporosis risk. In the present study, we performed a gene-based analysis of the largest GWASs in the bone field to identify additional BMD-associated genes. Methods BMD-associated genes were identified by combining the summary statistic P values of SNPs across individual genes in the two consecutive meta-analyses of GWASs from the Genetic Factors for Osteoporosis (GEFOS) studies. The potential functionality of these genes to bone was partially assessed by differential gene expression analysis. Additionally, the consistency of the identification of potential BMD-associated variants were evaluated by estimating the correlation of the P values of the same SNPs/genes between the two consecutive GEFOS studies with largely overlapping samples. Results Compared to the SNP-based analysis, the gene-based strategy identified additional BMD-associated genes with genome-wide significance and increased their mutual replication between the two GEFOS datasets. Among these BMD-associated genes, 3 novel genes (UBTF, AAAS, and C11orf58) were partially validated at the gene expression level. The correlation analysis presented a moderately high between-study consistency of potential BMD-associated variants. Conclusions Gene-based analysis as a supplementary strategy to SNP-based GWAS, when applied here, is shown that it helped identify some novel BMD-associated genes. In addition to its empirically increased statistical power, gene-based analysis also provides a higher testing stability for identification of BMD genes.

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SOST Polymorphisms and Response to Alendronate Treatment in Postmenopausal Chinese Women With Osteoporosis

Cited by 16 publications

References 37 publications

Expression of Sclerostin in Osteoporotic Fracture Patients Is Associated with DNA Methylation in the CpG Island of the SOST Gene

Expression of Sclerostin in Osteoporotic Fracture Patients Is Associated with DNA Methylation in the CpG Island of the SOST Gene

Genetic and acquired factors influencing the effectiveness and toxicity of drug therapy in osteoporosis

Gene-based GWAS analysis for consecutive studies of GEFOS

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