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Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease with high morbidity and mortality rates worldwide. Cytokines, which are the main regulators of immune responses, play crucial roles in inflammatory diseases such as COPD. Moreover, certain genetic variations can alter cytokine expression, and changes in cytokine level or function can affect disease susceptibility. Therefore, investigating the association between genetic variations and disease progression can be useful for prevention and treatment. Several studies have explored the association between common genetic variations in cytokine genes and COPD susceptibility. In this study, we summarized the reported studies and, where possible, conducted a systematic review and meta-analysis to evaluate the genetic association between various cytokines and COPD pathogenesis. We extracted relevant articles from PubMed and Google Scholar databases using a standard systematic search strategy. We included a total of 183 studies from 78 separate articles that evaluated 50 polymorphisms in 12 cytokine genes in this study. Our analysis showed that among all reported cytokine polymorphisms (including TNF-α, TGF-β, IL1, IL1RN, IL4, IL4R, IL6, IL10, IL12, IL13, IL17, IL18, IL27, and IL33), only four variants, including TNF-α-rs1800629, TGF-β1-rs6957, IL13-rs1800925, and IL6-rs1800796, were associated with the risk of COPD development. This updated meta-analysis strongly supports the association of TNF-α-rs1800629, TGF-β1-rs6957, IL13-rs1800925, and IL6-rs1800796 variants with a high risk of COPD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and Objective: TNF-α -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-α-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-α and COPD., Method: The published studies concerned the association between TNF-α 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-α 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%CI: (0.44-0.79), P < 0.00) compared to AA genotype carriers. In contrast, the AA genotype carriers of the TNF-α 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-α 308 gene variant as an independent factor in its pathogenesis opens new insights to diagnosis and management of COPD., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Interleukins are cytokines involved in systemic inflammation and immune system regulation. Many studies have investigated the association between common genetic variations in interleukin-coding genes and COPD susceptibility. In this study, a systematic review and meta-analysis was performed to evaluate the association between interleukin gene variations and COPD pathogenesis. Association studies were retrieved from PubMed and Google Scholar databases using the standard systematic search strategy. A total of 26 different studies evaluating eight polymorphisms in four interleukin genes were included in this study. In overall comparisons, IL1β-rs16944, -rs1143627, -rs1143634, IL13-rs20541 polymorphisms were found not to be associated with the increased risk for developing COPD. However, IL1RN-rs2234663 and IL13-rs1800925 showed a strong association with COPD. We showed that the CC genotype carriers of the IL6-rs1800795 are at significantly higher risk of developing COPD (OR = 1.31, 95% CI: 1.04-1.64, P = 0.01) compared to GG carriers. In case of IL6-rs1800796, individuals with CC and CG genotypes showed a lower risk to develop COPD (OR = 0.46, 95%CI: 0.32-0.66, P > 0.00). This updated meta-analysis strongly supports the association of IL1RN-rs2234663, IL6-rs1800795, -rs1800795 and IL13-rs1800925 variants with COPD., (Copyright © 2019 Elsevier Ltd. All rights reserved.)