Abstract
BackgroundOsteoarthritis (OA) is an important health issue in elderly people. Many studies have suggested that genetic factors are important risk factors for OA, of which tumor necrosis factor-α (TNF-α) is one of the most examined genes. Moreover, several studies have investigated the relationship between TNF-α G-308A polymorphisms and OA risk, but consistent results have not been obtained.ObjectiveThis study examines the association between TNF-α G-308A polymorphisms and knee OA. Moreover, meta-analysis and trial sequential analysis (TSA) was used to determine whether this is a susceptibility gene for knee OA.MethodsBetween 2015 and 2019, 591 knee OA cases and 536 healthy controls were recruited. The Kellgren–Lawrence grading system was used to identify the knee OA cases. A meta-analysis was conducted including related studies published until 2020 from PubMed, Embase, and previous meta-analysis to improve the evidence level of the current study. The results were expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) to evaluate the effect of this polymorphism on knee OA risk. The TSA was used to estimate the sample sizes required in this issue.ResultsA nonsignificant association was found between the AA genotype and knee OA [adjusted OR, 0.84; 95% CI, 0.62–1.15) in the recessive model] in the present case–control study, and analysis of other genetic models showed a similar trend. After adding the critical case–control samples for Asians, the TNF-α G-308A, AA genotype exhibited 2.57 times more risk of developing arthritis when compared with the GG + GA genotype (95% CI, 1.56–4.23), and the cumulative samples for TSA (n = 2182) were sufficient to obtain a definite conclusion.ConclusionsThe results of this meta-analysis revealed that the TNF-α G-308A, AA genotype is a susceptible genotype for OA in the Asian population. This study integrated all current evidence to arrive at this conclusion, suggesting that future studies on Asians are not required.
Highlights
Osteoarthritis (OA) is the most common joint disease that is the main cause of disability among elderly people globally [1]
A nonsignificant association was found between the AA genotype and knee OA [adjusted odds ratios (ORs), 0.84; 95% confidence intervals (CI), 0.62–1.15) in the recessive model] in the present case–control study, and analysis of other genetic models showed a similar trend
The cumulative samples for trial sequential analysis (TSA) (n = 2182) were sufficient to obtain a definite conclusion. The results of this meta-analysis revealed that the Tumor necrosis factor-α (TNF-α) G-308A, AA genotype is a susceptible genotype for OA in the Asian population
Summary
Osteoarthritis (OA) is the most common joint disease that is the main cause of disability among elderly people globally [1]. A previous study suggested that OA is primarily influenced by genetic risk factors due to common population polymorphisms in multiple genes [3]. Previous studies found that the expression level of TNF-α G-308A gene polymorphism has the highest correlation with OA [10] and that an increased OA risk prevails in the recessive genetic model, which only exists among the Asian population [11]. This study aimed to examine the relationship between TNF-α G-308A gene polymorphism and OA. Many studies have suggested that genetic factors are important risk factors for OA, of which tumor necrosis factorα (TNF-α) is one of the most examined genes. Several studies have investigated the relationship between TNF-α G-308A polymorphisms and OA risk, but consistent results have not been obtained
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