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Associations between OPG and RANKL polymorphisms, vertebral fractures, and abdominal aortic calcification in community-dwelling older subjects: the Sao Paulo Ageing & Health Study (SPAH)

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Abstract

Summary

This is the first study analyzing concomitantly osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL) polymorphisms and OPG/RANKL serum levels and their association with bone mineral density (BMD), vertebral fractures, and vascular aortic calcification in a cohort of 800 subjects in community-dwelling older individuals.

Introduction

Osteoprotegerin (OPG) and RANKL play an important role in osteoclast activation and differentiation as well as in vascular calcification. At present, there are no studies of OPG or RANKL gene polymorphisms in Brazilian older populations. The aim of this study was to evaluate OPG/RANKL polymorphism and their association with vertebral fractures (VFs) and aortic calcification.

Methods

Eight hundred subjects (497 women/303 men) were genotyped for the OPG 1181G>C (rs2073618), 163C>T (rs3102735), 245T>G (rs3134069), and 209G>A (rs3134070) and RANKL A>G (rs2277438) single-nucleotide polymorphisms (SNPs). VFs were evaluated by spine radiography (Genant’s method). Aortic calcification was quantified using Kauppila’s method.

Results

The isolated genotype analyses and single-allele frequency data showed association of OPG 163C, 245G, and 209A alleles with presence of VFs (P < 0.05). Multiple logistic regression of subjects with absence of VFs vs. those with VFs (grades II/III) revealed only OPG 209A homozygosity as a risk factor for higher-grade VFs (odds ratio (OR) = 4.17, 95 % CI 1.03–16.93, P = 0.046). Regarding aortic calcification, the isolated genotype analysis frequency data revealed a significant association of OPG 1181G, 163C, 245G, and 209A alleles with absent aortic calcification (P < 0.05). Multiple logistic regression data confirmed that the OPG 209A allele was protective for aortic calcification (OR = 0.63, 95 % CI 0.45–0.88, P = 0.007) and the OPG 1181C allele was a risk factor for aortic calcification (OR = 1.26, 95 % CI 1.00–1.58, P = 0.046).

Conclusion

This study showed that the OPG 209AA genotype was a risk factor for higher-grade VFs, the OPG 209A allele was protective for aortic calcification, and the OPG 1181C was a risk factor for aortic calcification, supporting the involvement of OPG polymorphisms in the analyzed phenotypes and the concept that the related pathogenesis is multifactorial.

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Acknowledgments

We thank Liliam Takayama for technical support and Jaqueline B. Lopes for her help in collected data.

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Authors and Affiliations

  1. Bone Metabolism Laboratory, Rheumatology Division, Faculdade de Medicina da Universidade de São Paulo, Av, Dr Arnaldo, 455, 3° andar Reumatologia, sala 3193, São Paulo, SP, 01246-903, Brazil

    R. M. R. Pereira, C. P. Figueiredo, C. C. Cha, V. F. Caparbo & A. S. Franco

  2. RDO Diagnosticos Medicos, São Paulo, São Paulo, Brazil

    R. M. Oliveira

  3. Department of Preventive Medicine, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

    P. R. Menezes

  4. Molecular Medicine, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

    I. de Castro

  5. Divisions of Nephrology and Molecular Medicine, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

    L. F. Onuchic

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  1. R. M. R. Pereira
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  2. C. P. Figueiredo
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  3. C. C. Cha
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Correspondence to R. M. R. Pereira.

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Funding

This work was supported by the following organizations and grants: Fundação de Amparo e Pesquisa do Estado de São Paulo (FAPESP no. 03/09313-0 and no. 09/11755-7), Conselho Nacional de Ciência e Tecnologia (CNPQ no. 472754/2013-0 to RMRP), Federico Foundation (to RMRP), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES to CPF).

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Pereira, R.M.R., Figueiredo, C.P., Cha, C.C. et al. Associations between OPG and RANKL polymorphisms, vertebral fractures, and abdominal aortic calcification in community-dwelling older subjects: the Sao Paulo Ageing & Health Study (SPAH). Osteoporos Int 27, 3319–3329 (2016). https://doi.org/10.1007/s00198-016-3664-x

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