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



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.



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.



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).



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.
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. rosamariarp@yahoo.com.
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Pereira
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.
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Figueiredo
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.
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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.
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Caparbo
RDO Diagnosticos Medicos, São Paulo, São Paulo, Brazil.
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Oliveira
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.
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Franco
Department of Preventive Medicine, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
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Menezes
Molecular Medicine, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
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de Castro
Divisions of Nephrology and Molecular Medicine, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
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Onuchic
D000368:Aged; D000375:Aging; D001011:Aorta / Q000473:pathology*; D015519:Bone Density; D001938:Brazil; D002114:Calcinosis / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D053244:Osteoprotegerin / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D053245:RANK Ligand / Q000097:blood / Q000235:genetics*; D016103:Spinal Fractures / Q000235:genetics*
D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human
Aortic calcification; Osteoprotegerin; Polymorphism; RANKL; Vertebral fractures