RANKL and OPG gene polymorphisms: associations with vertebral fractures and bone mineral density in premenopausal systemic lupus erythematosus

Bonfa, Alessandra C.; Seguro, Luciana Parente Costa; Caparbo, Valéria F.; Bonfá, Eloísa; Pereira, Rosa Maria Rodrigues

doi:10.1007/s00198-015-3029-x

Cited by 42 publications

(29 citation statements)

References 36 publications

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“…1). Finally, a total of 10 studies were enrolled in this meta-analysis 8, 10–15, 23–25 , and a total of 12 SNPs with genotyping data in at least one study were meta-analyzed. Supplementary Table 2 listed the detailed information of recruited studies for this meta-analysis, i .…”

Section: Resultsmentioning

confidence: 99%

“…For example, one recent published GWAS using European and east Asian cohorts identified 56 loci associated with BMD which surpassed genome-wide significance ( P < 5E-08), and 14 SNPs among them showed significant association with fracture risk 7 . However, candidate association studies of BMD or osteoporotic fracture focusing on bone remodeling related genes have produced conflicting results in different populations 8, 15 . Discordant results may be due to different populations or limited sample size used in previous studies.…”

Section: Discussionmentioning

confidence: 99%

“…Several groups have tested the association of OPG variation with osteoporosis susceptibility; however the results remain largely inconsistent. Studies conducted in Brazilian, American, Chinese, Slovakian samples have resulted in positive results 10–13 ; while other groups using Icelandic, Australian, Brazilian and Chinese cohorts have failed to replicate this association 8, 14, 15 . Given the inconsistent association result, whether OPG variants are associated with osteoporosis remains illusive.…”

Section: Introductionmentioning

confidence: 97%

“…Most of these genes are known to influence bone physiology, specifically the reabsorption of bone by osteoclasts and the formation of bone by osteoblasts. Those genes include but not limited to ESR1 , COL1A1 , LRP5 , RANKL , OPG , SLC25A13 , etc 5–8 . Nevertheless, all the identified risk variants could only explain a small portion of heritability of osteoporosis, and many more variants remain to be identified.…”

Section: Introductionmentioning

confidence: 99%

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Common Variants in OPG Confer Risk to Bone Mineral Density Variation and Osteoporosis Fractures

Sheng

Cai

Gong

et al. 2017

Sci Rep

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Although many common variants have been identified for bone mineral density (BMD) and osteoporosis fractures, all the identified risk variants could only explain a small portion of heritability of BMD and osteoporosis fractures. OPG belongs to the tumor necrosis factor receptor superfamily, which plays a crucial role in bone remodeling and is thus a promising candidate gene of osteoporosis. Several studies have explored the association of OPG variants with BMD or osteoporosis fractures, however, the results remain inconsistent among different populations. In the study, we first assessed the relationship between OPG variants and BMD or osteoporosis fractures in our sample size (227 subjects with postmenopausal osteoporosis and 189 controls), and then performed a systematic meta-analysis. Among the nine SNPs genotyped, rs6469804 and rs2073618 showed significant associations with both BMD and osteoporotic fractures, while rs3102735 was only associated with BMD in our samples (P < 0.05). For meta-analyses, data for a total of 12 SNPs were pooled (4725 patients and 37804 controls), and five SNPs, including rs6993813, rs6469804, rs3134070, rs2073618 and rs3102734, showed association with osteoporosis fractures (P < 0.05). On light of the above analysis, we believe that OPG is one promising susceptibility gene of BMD or osteoporotic fractures.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Common Variants in OPG Confer Risk to Bone Mineral Density Variation and Osteoporosis Fractures

Sheng

Cai

Gong

et al. 2017

Sci Rep

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“…The analysis of OPG gene variants C950T (promoter) and C1181G (exon 1) revealed that the presence of polymorphic 1181G/950T alleles and 950 TT/1181 GG genotypes may play a role in the development of bone disease [95]. Apart from breast cancer, genetic variations in form of polymorphisms in OPG and RANKL have also been associated with bone fractures in premenopausal patients with systemic lupus erythematosis (SLE) [96]. OPG/A163G polymorphism has been suggested to contribute to the genetic regulation of bone mineral density or bone turnover markers in Slovak population and thus could increase or decrease osteoporosis risk [97].…”

Section: Opg and Genetic Polymorphismmentioning

confidence: 99%

Osteoprotegerin rich tumor microenvironment: implications in breast cancer

Goswami

Sharma-Walia

2016

Oncotarget

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Osteoprotegerin (OPG) is a soluble decoy receptor for tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL). It belongs to the tumor necrosis factor receptor superfamily (TNFRSF). OPG was initially discovered to contribute to homeostasis of bone turnover due to its capability of binding to receptor activator of nuclear factor-kappaB (NF-kB). However, apart from bone turnover, OPG plays important and diverse role(s) in many biological functions. Besides having anti-osteoclastic activity, OPG is thought to exert a protective anti-apoptotic action in OPG-expressing tumors by overcoming the physiologic mechanism of tumor surveillance exerted by TRAIL. Along with inhibiting TRAIL induced apoptosis, it can induce proliferation by binding to various cell surface receptors and thus turning on the canonical cell survival and proliferative pathways. OPG also induces angiogenesis, one of the hallmarks of cancer, thus facilitating tumor growth. Recently, the understanding of OPG and its different roles has been augmented substantially. This review is aimed at providing a very informative overview as to how OPG affects cancer progression especially breast cancer.

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Rheumatic Diseases and Osteoporosis

Munno

Malavolta

Minisola

2018

Multidisciplinary Approach to Osteoporosis

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RANKL and OPG gene polymorphisms: associations with vertebral fractures and bone mineral density in premenopausal systemic lupus erythematosus

Abstract: Our study provides novel data demonstrating that RANKL/OPG genetic variations appear to play a role in bone remodeling, particularly in its major complication, fracture, in premenopausal patients with SLE.

Cited by 42 publications

References 36 publications

Common Variants in OPG Confer Risk to Bone Mineral Density Variation and Osteoporosis Fractures

Common Variants in OPG Confer Risk to Bone Mineral Density Variation and Osteoporosis Fractures

Osteoprotegerin rich tumor microenvironment: implications in breast cancer

Rheumatic Diseases and Osteoporosis

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