Association Between TNF-α-308, +489, -238 Polymorphism, and COPD Susceptibility: An Updated Meta-Analysis and Trial Sequential Analysis.

Zhiyu Xia,Yufei Wang,Fu Liu,Hongxin Shu,Peng Huang

doi:10.3389/fgene.2021.772032

Abstract

The tumor necrosis factor alpha (TNF-α) polymorphism may play an important role in chronic obstructive pulmonary disease (COPD) susceptibility. However, the results are still inconclusive. Eligible studies were searched in Cochrane Library database, EMBASE, Pudmed, Web of science, China National Knowledge Infrastructure, and Wanfang database. Finally, a total of 27 case-control studies with 3473 COPD cases and 4935 controls were included in the present analysis. We also performed trial sequential analysis (TSA) to confirm our results. Overall, association between TNF-α-308G/A polymorphism and COPD susceptibility was identified in allelic model (A vs. G, OR = 1.21, 95%CI: 1.01–1.45, p = 0.04) when smoking status was not adjusted. In ethnicity subgroup analysis, we found that the TNF-α -308G/A polymorphism was associated to COPD among Asians (GA vs. GG, OR = 1.35, 95%CI: 1.04–1.77, p = 0.02) when smoking status was not adjusted. However, no significant association was found in Asian smokers or Caucasian smokers. In conclusion, our study suggest that TNF-α-308 GA genotype is related to COPD in the Asian population. In addition, the TNF-α+489G/A, - 238G/A variants do not increase the risk of COPD. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021273980.

Highlights

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction and bronchial hyperresponsiveness, with increasing morbidity, mortality, and resource utilization worldwide (Celli et al, 2015)
In the stratified analysis by ethnicity, we found that the TNF-α-308 G/A polymorphism was associated with COPD risk under the allelic model (A vs. G, odds rations (ORs) 1.40, 95% confidence intervals (CIs): 1.03–1.89, p 0.03)
For the TNF-α-308 G/A, the GA genotype was significantly associated with increased COPD risk, especially among Asians

Summary

INTRODUCTION

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction and bronchial hyperresponsiveness, with increasing morbidity, mortality, and resource utilization worldwide (Celli et al, 2015). The signals are mediated through two transmembrane receptors, TNFR1 and TNFR2, to regulate the inflammatory cell functions such as cell proliferation, survival, TNF-α: Risk Factors for COPD differentiation, and apoptosis (Parameswaran and Patial, 2010). Some epidemiologic research on the association between TNFα+489 G/A and -308 G/A polymorphism and COPD susceptibility have been performed (Cui et al, 2015; Zhang et al, 2016; Reséndiz-Hernández et al, 2018; Yu et al, 2021), but the results are still inconsistent. The scarcity of meta-analysis about the relationship between TNF-α-238G/A and COPD risk impels us to study the issue in this article. Subgroup analysis based on ethnicity was performed to gain a comprehensive view

Literature Retrieval

RESULTS

DISCUSSION

Participants included

DATA AVAILABILITY STATEMENT