TNF-α-308 G/A variant and susceptibility to chronic obstructive pulmonary disease: A systematic review and meta-analysis

Background and objective: TNF-alpha 308 G/A variant is recognized to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Although many studies have investigated the association of TNF-alpha 308 and COPD risk, a deep understanding of this association is lacking due to small subjects sizes and insufficiently study designs among different investigations. In this study, a systematic review and meta-analysis was performed based on published reports on the association of TNF-alpha and COPD. Method: The published studies concerned the association between TNF-alpha and COPD were identified using a systematic research in Scopus, Google Scholar, and PubMed up to April 2018. A total of 46 different papers studying the rs1800629 variant in TNF-alpha gene were included. Then, human studies were selected to further analysis regardless of papers language. Results: Based on the results, the major outcome of this meta-analysis can be represented as follows: individuals with GG and GA genotypes possess less risk of developing COPD (OR = 0.58, 95%Cl: (0.44-0.79), P < 0.00) compared to AA genotype carriers. In contrast, the AA genotype carriers of the TNF-alpha rs1800629 has a significantly higher risk of developing COPD (OR = 1.83, 95%CI: (1.34-2.51), P < 0.00) compared to GG carrier. Despite the previous meta-analysis results which reported significantly decreasing of heterogeneity with ethnicity, we found that the source of controls has a significant contribution to observed heterogeneity. Conclusions: Thanks to the global burden of COPD studies, proving TNF-alpha 308 gene variant as an independent factor in its pathogenesis opens new insights to diagnosis and management of COPD.