ABSTRACT
BACKGROUND: Osteoarthritis (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. AIM: This 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. METHODS: This 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). METHODS: The 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. RESULTS: TNFA 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)]. CONCLUSION: We conclude that the SNP - 308 G/A of TNFA gene may affect osteoarthritis susceptibility, severity and functional status of individuals with osteoarthritis.
Subject(s)
Osteoarthritis, Hip/genetics , Osteoarthritis, Knee/genetics , Osteoarthritis/genetics , Physical Functional Performance , Polymorphism, Single Nucleotide , Severity of Illness Index , Tumor Necrosis Factor-alpha/genetics , Aged , Aged, 80 and over , Alleles , Case-Control Studies , Female , Genetic Predisposition to Disease , Genotype , Humans , Male , Middle Aged , Osteoarthritis/diagnostic imaging , Osteoarthritis/physiopathology , Osteoarthritis, Hip/diagnostic imaging , Osteoarthritis, Hip/physiopathology , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/physiopathology , Real-Time Polymerase Chain ReactionABSTRACT
Abstract Background: Osteoarthritis (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. Aim: This 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. Methods: This 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). Methods: The 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. Results: TNFA 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)]. Conclusion: We conclude that the SNP - 308 G/A of TNFA gene may affect osteoarthritis susceptibility, severity and functional status of individuals with osteoarthritis.
