Association between single-nucleotide polymorphism of cytokines genes and chronic obstructive pulmonary disease: A systematic review and meta-analysis

Cytokine. 2023 Nov:171:156352. doi: 10.1016/j.cyto.2023.156352. Epub 2023 Sep 11.


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.

Keywords: Chronic obstructive pulmonary disease; Cytokine; Meta-analysis; Variant.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review

MeSH terms

  • Cytokines / genetics
  • Genetic Predisposition to Disease
  • Humans
  • Interleukin-13 / genetics
  • Interleukin-6 / genetics
  • Polymorphism, Single Nucleotide* / genetics
  • Pulmonary Disease, Chronic Obstructive* / genetics
  • Transforming Growth Factor beta1 / genetics
  • Tumor Necrosis Factor-alpha / genetics


  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • Interleukin-13
  • Interleukin-6
  • Cytokines