Functional status and severity of osteoarthritis in elderly is associated to the polymorphism of TNFA gene

Marcos Tadeu Parron Fernandes,Walquíria Shimoya-Bittencourt,Fernanda Freitas Anibal,Regina Célia Poli-Frederico,Karen Barros Parron Fernandes,Viviane Martins Santos,Priscila Daniele De Oliveira Perrucini

doi:10.1186/s42358-019-0068-6

Abstract

BackgroundOsteoarthritis (OA) is a major musculoskeletal disease with high prevalence in the elderly. The study of genetic polymorphisms of inflammatory mediators involved in OA may contribute to the elucidation of the complex pathophysiology of this disease and identification of susceptibility individuals.AimThis study aimed to evaluate the association between polymorphism at tumor necrosis factor alpha gene (SNP - 308 G/A TNFA) with presence, severity and functional status of osteoarthritis in elderly.MethodsThis study was characterized as case-control and encompassed 257 physically independent elderly (Mean Age: 68.55 ± 5.2; Minimum age: 60 and Maximum age: 82) were recruited. After this selection, the groups were divided in: 92 elderly individuals with osteoarthritis (case group) and 165 without the disease (control group).MethodsThe individuals were genotyped by the TaqMan real-time PCR system. The subjects were classified based on the degree of radiological impairment according to the criteria of Kellgren-Laurence and regarding functional impairment using the WOMAC and LEQUESNE questionnaires.ResultsTNFA gene polymorphic individuals (subjects harboring allele A) are more affected by OA (χ2 = 8.7, p = 0.003), once they have major radiological lesion both in hip (Fisher-Freeman-Halton Test = 3.9, p = 0.04) and knee (Fisher-Freeman-Halton Test = 4.0, p = 0.04) as well as worse functional status assessed by the Lequesne questionnaire (Mann-Whitney, p = 0.04). At the multivariate analysis, after adjustment for age, gender, body mass index, the presence of rare allele for TNFA (allele A) increases the susceptibility to OA development [OR: 1.87 (95% CI: 1.1–3.2)].ConclusionWe conclude that the SNP − 308 G/A of TNFA gene may affect osteoarthritis susceptibility, severity and functional status of individuals with osteoarthritis.

Highlights

Osteoarthritis (OA) is the most prevalent osteomuscular disease as well as the most common form of arthritis
The inflammation usually results from biomechanical stress, changes in chondrocyte function related to the aging process, and dysregulation of inflammatory cytokine activity [8, 9]
Among the main mediators is tumor necrosis factor alpha (TNF-A), called proinflammatory cytokine, which play a central role in the pathophysiology of OA [10]

Summary

Introduction

Osteoarthritis (OA) is the most prevalent osteomuscular disease as well as the most common form of arthritis It mainly affects elderly individuals, being a significant cause of limitations and incapacities at this population [1, 2]. Among the main mediators is tumor necrosis factor alpha (TNF-A), called proinflammatory cytokine, which play a central role in the pathophysiology of OA [10]. It is produced by chondrocytes, mononuclear cells, osteoblasts and synovial tissue, and act synergistically regulate the synthesis of components of the extracellular matrix by inhibiting the anabolic activity, and stimulation of production and release of catabolic inflammatory factors [11]. The study of genetic polymorphisms of inflammatory mediators involved in OA may contribute to the elucidation of the complex pathophysiology of this disease and identification of susceptibility individuals

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