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

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Abstract

Summary

Premenopausal women with systemic lupus erythematosus (SLE) have a higher prevalence of low bone mineral density and vertebral fractures. Multiple genetic loci for osteoporotic fracture were identified in recent genome-wide association studies. This study provides a novel data demonstrating that receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) polymorphisms likely plays an important role in the bone remodeling process in SLE premenopausal women.

Introduction

The purpose of this study was to evaluate single-nucleotide polymorphisms (SNPs) of the RANKL, RANK, and OPG genes in premenopausal SLE patients and their association with sRANKL and OPG serum levels, vertebral fractures, and bone mineral density (BMD).

Methods

A total of 211 premenopausal SLE patients (American College of Rheumatology (ACR) criteria) and 154 healthy controls were enrolled. SNPs of RANKL 290A>G (rs2277438), OPG 1181G>C (rs2073618), 245T>G (rs3134069), 163A>G (rs3102735), and RANK A>G (rs3018362) were obtained by real-time PCR. sRANKL/OPG serum levels were determined by ELISA. BMD and vertebral fractures were evaluated by dual-energy X-ray absorptiometry (DXA).

Results

SLE patients and controls had similar frequencies of the RANKL 290 G allele (p = 0.94), OPG 1181 C allele (p = 0.85), OPG 245 G allele (p = 0.85), OPG 163 G allele (p = 0.78), and RANK G allele (p = 0.87). Further analysis of the SLE patients revealed that the frequency of the RANKL 290 G allele was lower in patients with fractures than that in patients without fractures (28.1 vs 46.9 %, p = 0.01). In addition, the frequency of the OPG 245 G allele was higher in patients with low BMD than that in patients with normal BMD (31.4 vs 18.1 %, p = 0.04). No association of OPG 1181 G>C, OPG 163 A>G, and RANK A>G SNPs with BMD/fractures was found. Additionally, no association was observed between RANKL/OPG/RANK SNPs and sRANKL/OPG serum levels.

Conclusions

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.

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Acknowledgments

We thank Jackeline C Alvarenga and Liliam Takayama for technical support and Dr Rogerio Ruscitto for statistical analysis.

Funding

This study was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ #301805/2013-0 and #472754/2013-0 to RMRP and #301411/2009-3 to EB) and Federico Foundation (to RMRP and EB) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES to ACB).

Conflicts of interest

Alessandra C Bonfa, Luciana PC Seguro, Valeria F Caparbo, Eloisa Bonfa, and Rosa Maria Rodrigues Pereira declare that they have no conflict of interest.

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Authors and Affiliations

  1. Rheumatology Division, Faculdade Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455, 3 andar, Sala, 3105, São Paulo, Brazil

    A. C. Bonfá, L. P. C. Seguro, V. Caparbo, E. Bonfá & R. M. R. Pereira

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  1. A. C. Bonfá
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  2. L. P. C. Seguro
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  3. V. Caparbo
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  4. E. Bonfá
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  5. R. M. R. Pereira
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Correspondence to R. M. R. Pereira.

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Bonfá, A.C., Seguro, L.P.C., Caparbo, V. et al. RANKL and OPG gene polymorphisms: associations with vertebral fractures and bone mineral density in premenopausal systemic lupus erythematosus. Osteoporos Int 26, 1563–1571 (2015). https://doi.org/10.1007/s00198-015-3029-x

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  • DOI: https://doi.org/10.1007/s00198-015-3029-x

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