Quantitative Assessment of the Association between Polymorphisms in Osteoprotegerin Gene and Risk of Low Bone Mineral Density

Felipe Rodolfo Pereira Da Silva,Larissa Dos Santos Pessoa,Geofabio Sucupira Casimiro,Antonio De Pádua Rocha Nóbrega Neto,Daniel Fernando Pereira Vasconcelos,Any Carolina Cardoso Guimarães Vasconcelos

doi:10.3823/1768

Abstract

Background: Low bone mineral density (BMD) predisposes to osteoporosis and elevated risk of fractures. Osteoprotegerin is a soluble molecule associated to metabolism of bone tissue with inhibition of osteoclast-differentiation. Several studies determined the relation among polymorphisms in osteoprotegerin gene and low BMD, but the results are contradictory, so an evaluation about these polymorphisms is necessary. This study carried out a meta-analysis to four polymorphisms in osteoprotegerin gene (A163G, G1181C, T950C, T245G).Methods: A search in literature was made to identify studies with relevant information. The data was extracted by two investigators independently, following a standardized form. The statistical software Review Manager version 5.2 was used to calculation of heterogeneity (I²), Odds Ratio (OR) and Funnel plots with P<0.05.Results: Nineteen papers with twenty-one eligible studies with 5,120 patients and 4,386 controls were identified. G allele was associated to case group in A163G, G1181C and T245G polymorphisms (OR = 1.27, 95% CI 1.10, 1.46, P = 0.0010; OR = 1.25, 95% CI 1.14, 1.37, P < 0.00001; OR = 1.24, 95% CI 1.05, 1.48, P = 0.01, respectively). In T950C polymorphism, T allele neither C allele was associated to risk of bone low mineral density. No bias of publication was found in this analysis.Conclusion: This meta-analysis with 5,120 patients with low bone mineral density and 4,386 controls showed significant association among G alleles in A163G, G1181C and T245G polymorphism and increased risk of low BMD, T950C polymorphism was not significantly associated to risk of low bone mineral density.

Highlights

Low bone mineral density is a clinical condition present in common diseases such as osteoporosis, and is the single best predictor of osteoporotic fractures and a valuable tool in the evaluation of fracture risk [1].Studies on twins and on families have shown that as much as 70–80% of the inter-individual variance in bone mineral density at the spine and hip is genetically determined
Strategy of search A systematic search in literature was performed by three investigators in the electronic biomedical and education databases (Cochrane Library, Google Scholar, MEDLINE and PubMed) to studies published before March 11, 2015 and addressing the association of A163G, G1181C, T245G and T950C polymorphisms in OPG gene and Low Bone Mineral Density
Inclusion criteria Articles were included in current meta-analysis if the studies met all the following criteria: (1) Eva-This article is available at: www.intarchmed.com and www.medbrary.com luation of the polymorphisms cited and risk of low bone mineral density; (2) Studies are case/control design; (3) Genotype frequency documented; (4) Diagnosis of low bone mineral density confirmed through radiographic findings and clinical evaluation; (5) The distributions of alleles in study meet in Hardy-Weinberg Equilibrium (HWE)

Summary

Introduction

Low bone mineral density is a clinical condition present in common diseases such as osteoporosis, and is the single best predictor of osteoporotic fractures and a valuable tool in the evaluation of fracture risk [1].Studies on twins and on families have shown that as much as 70–80% of the inter-individual variance in bone mineral density at the spine and hip is genetically determined. Several genes have been evaluated to assess their involvement in low BMD [3,4,5] and the osteoprotegerin (OPG) gene is one of the most important candidate genes for osteoporosis, suggested to be associated with low BMD and risk of fractures [6]. The recent studies focus in four polymorphisms in OPG gene: A163G, G1181C, T950C and T245G. These variations already were associated to low Bone Mineral Density [8] and osteoporosis [9]. Low bone mineral density (BMD) predisposes to osteoporosis and elevated risk of fractures. Several studies determined the relation among polymorphisms in osteoprotegerin gene and low BMD, but the results are contradictory, so an evaluation about these polymorphisms is necessary. This study carried out a meta-analysis to four polymorphisms in osteoprotegerin gene (A163G, G1181C, T950C, T245G)

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