Genetic Variations in Genes Encoding RANK, RANKL, and OPG in Rheumatoid Arthritis: A Case-Control Study

Aßmann, Gunter; Koenig, Jochem; Pfreundschuh, Michael; Epplen, Jörg T.; Kekow, J; Roemer, Klaus; Wieczorek, Stefan

doi:10.3899/jrheum.091110

Cited by 40 publications

(36 citation statements)

References 18 publications

(19 reference statements)

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“…However, the RA group showed significantly higher serum levels of RANKL, a higher RANKL/OPG ratio, and a lower serum level of OPG than the controls in the study. A German article also reported that OPG rs3102735 T/C and rs2073618 G/C polymorphisms showed no significant difference between patients with RA and healthy controls in a Caucasian population (Assmann et al, 2010). Thus, it appears that OPG rs3102735 T/C and rs2073618 G/C polymorphisms are not associated with the risk for RA in Asian or Caucasian populations, indicating that the correlation between the two SNPs and RA may not be associated with ethnicity.…”

Section: Discussionmentioning

confidence: 99%

“…Several SNPs in the RANKL gene and the OPG gene, which might influence the binding of transcription factors, have been reported to be significantly associated with bone metabolism and susceptibility to RA (Kim et al, 2007;Assmann et al, 2010). The OPG gene encodes a known regulator of bone remodeling and maintains a fine balance between bone formation and resorption, involving osteoblasts and osteoclasts, and thus potentially contributes to the pathophysiology of osteoporosis (Simonet et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…Many studies have investigated the association between OPG polymorphisms and RA (Furuya et al, 2007;Assmann et al, 2010;Xu et al, 2014). Furuya et al (2007) conducted the first study of the OPG SNP rs2073618 and found no significant correlation with RA severity in Japanese patients.…”

Section: Discussionmentioning

confidence: 99%

“…Furuya et al (2007) revealed that the OPG gene polymorphism rs2073618 was not associated with the amount of joint destruction in early RA in Japanese patients. Two studies from Germany and China also indicated that OPG rs3102735 T/C and rs2073618 G/C polymorphisms were not related to RA (Assmann et al, 2010;Xu et al, 2014). Hence, we hypothesized that the OPG rs3102735 T/C and rs2073618 G/C polymorphisms were not associated with RA.…”

Section: Itroductionmentioning

confidence: 98%

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Osteoprotegerin polymorphisms in Chinese Han patients with rheumatoid arthritis

2015

Genet. Mol. Res.

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ABSTRACT. In order to investigate the association between osteoprotegerin (OPG) gene polymorphisms and rheumatoid arthritis (RA), we studied OPG rs3102735 T/C and rs2073618 G/C polymorphisms in a Chinese Han population comprising 574 patients with RA and 804 controls. Genotyping by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was conducted. Our data indicated that OPG rs3102735 T/C and rs2073618 G/C polymorphisms were not associated with the risk of RA. However, among older patients (≥55 years), patients with the OPG rs3102735 TC (TC vs TT: OR = 0.68, 95%CI = 0.49-0.96, P = 0.029) and TC/CC (TC+CC vs TT: OR = 0.69, 95%CI = 0.49-0.96, P = 0.026) genotypes showed a significantly lower risk of RA than patients with the TT genotype, while patients with the OPG rs2073618 GC (GC vs GG: OR = 1.53, 95%CI = 1.13-2.07, P = 0.006) and GC/CC (GC+CC vs GG: OR = 1.43, 95%CI = 1.07-1.92, P = 0.015) genotypes showed a significantly higher risk of RA than patients with the GG genotype. We

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Itroductionmentioning

confidence: 98%

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Osteoprotegerin polymorphisms in Chinese Han patients with rheumatoid arthritis

2015

Genet. Mol. Res.

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“…Another study implied some role in longevity [45]. Other studies examining femoral neck compression strength [46], susceptibility to rheumatoid arthritis [47], or breast cancer [48] did not see any association.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the RANK/RANKL genes and their effect on bone specific prognosis in breast cancer patients

Hein¹,

Bayer²,

Schrauder³

et al. 2014

Geburtshilfe Frauenheilkd

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The receptor activator of NF-B (RANK) pathway is involved in bone health as well as breast cancer (BC) pathogenesis and progression. Whereas the therapeutic implication of this pathway is established for the treatment of osteoporosis and bone metastases, the application in adjuvant BC is currently investigated. As genetic variants in this pathway have been described to influence bone health, aim of this study was the prognostic relevance of genetic variants in RANK and RANKL. Single nucleotide polymorphisms in RANK(L) (rs1054016/rs1805034/rs35211496) were genotyped and analyzed with regard to bone metastasis-free survival (BMFS), disease-free survival, and overall survival for a retrospective cohort of 1251 patients. Cox proportional hazard models were built to examine the prognostic influence in addition to commonly established prognostic factors. The SNP rs1054016 seems to influence BMFS. Patients with two minor alleles had a more favorable prognosis than patients with at least one common allele (HR 0.37 (95% CI: 0.17, 0.84)), whereas other outcome parameters remained unaffected. rs1805034 and rs35211496 had no prognostic relevance. The effect of rs1054016(RANKL) adds to the evidence that the RANK pathway plays a role in BC pathogenesis and progression with respect to BMFS, emphasizing the connection between BC and bone health.

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A functional RANKL polymorphism associated with younger age at onset of rheumatoid arthritis

Tan¹,

Wu²,

Zhao³

et al. 2010

Arthritis & Rheumatism

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Objective. We previously observed the association of the co-occurrence of the HLA-DRB1 shared epitope (SE) and RANKL single-nucleotide polymorphisms (SNPs) with younger age at the onset of rheumatoid arthritis (RA) in 182 rheumatoid factor (RF)-positive European American patients with early-onset RA. The aim of this study was to fine-map the 48-kb RANKL region in the extended cohort of 210 European American RF-positive patients with early RA, to seek replication of RA-associated SNPs in additional RA cohorts of 501 European Americans and 298 African Americans, and to explore the functional consequences of RAassociated SNPs.Methods. SNP genotyping was conducted using pyrosequencing or TaqMan polymerase chain reaction (PCR) assays. Associations of rs7984870 with RANKL expression in plasma, peripheral blood mononuclear cells, and isolated T cells were quantified using enzymelinked immunosorbent assay and reverse transcription-PCR. Site-directed mutagenesis of rs7984870 within the 2-kb RANKL promoter was performed to drive the luciferase reporter gene in osteoblast and stromal cell lines. Interaction of DNA and protein was determined by electrophoretic mobility shift assay.Results. A single promoter SNP, rs7984870, was consistently significantly associated with earlier age at the onset of RA in 3 independent seropositive (RF or anti-cyclic citrullinated peptide antibody) RA cohorts but not in seronegative RA patients. The C risk allele of rs7984870 conferred 2-fold higher plasma RANKL levels in RF-positive patients with RA, significantly elevated RANKL messenger RNA expression in activated normal T cells, and increased promoter activity after stimulation in vitro via differential binding to the transcription factor SOX5.Conclusion. The RANKL promoter allele that increased transcription levels upon stimulation might promote interaction between activated T cells and dendritic cells, predisposing to a younger age at the onset of RA in seropositive European American and African American patients.Dr.

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Genetic Variations in Genes Encoding RANK, RANKL, and OPG in Rheumatoid Arthritis: A Case-Control Study

Abstract: The minor allele of the RANK SNP rs35211496 may be protective against RA, while the minor alleles of the RANKL SNP rs2277438 may increase susceptibility to RA.

Cited by 40 publications

References 18 publications

Osteoprotegerin polymorphisms in Chinese Han patients with rheumatoid arthritis

Osteoprotegerin polymorphisms in Chinese Han patients with rheumatoid arthritis

Polymorphisms in the RANK/RANKL genes and their effect on bone specific prognosis in breast cancer patients

A functional RANKL polymorphism associated with younger age at onset of rheumatoid arthritis

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