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Correlation between TNF-α -308 and +489 Gene Polymorphism and Acute Exacerbation of Chronic Obstructive Pulmonary Diseases.

ABSTRACT: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is becoming a common respiratory disease, leading to increased morbidity and mortality worldwide. Tumor necrosis factor-alpha (TNF-α) is a powerful proinflammatory cytokine involved in the pathogenesis of AECOPD. Therefore, we proposed a close correlation between the TNF-α polymorphism [-308G/A (rs1800629), +489G/A (rs1800610)] and the disease progress of patients with AECOPD. Comparison of the TNF-α genotypes between the 198 AECOPD diagnosed patients groups and 195 healthy peoples suggested their significant differences of the three genotypes (AA, GA, GG) distribution for TNF-α -308 (P < 0.05), but no differences of that for TNF-α +489. We found that patients with TNF-α -308 GA/AA genotypes showed smaller adjacent arterial diameter, thicker bronchial wall, higher bronchial artery ratio, higher bronchial wall grading, and higher frequency of acute exacerbations than those with TNF-α -308 GG genotype. Patients with TNF-α +489 GA/AA genotypes showed the same AECOPD properties as patients with TNF-α -308 except for the high frequency of acute exacerbations. Further experiment showed that the TNF-α -308 and+489 gene polymorphisms could affect the expression level of TNF-α in macrophages, suggesting the involvement of the macrophage population in disease regulation of AECOPD patients with TNF-α -308G/A and+489G/A genotype heterogeneity. In conclusion, the TNF-α -308 G/A genotype was related to AECOPD susceptibility and progress, while the TNF-α +489G/A genotype was related to AECOPD progress, but not AECOPD susceptibility.

SUBMITTER: Yu S

PROVIDER: S-EPMC7943264 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Correlation between TNF-α -308 and +489 Gene Polymorphism and Acute Exacerbation of Chronic Obstructive Pulmonary Diseases.

Yu Suyun S Xue Min M Yan Zhijun Z Song Bin B Hong Haiping H Gao Xiwen X

BioMed research international 20210301

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is becoming a common respiratory disease, leading to increased morbidity and mortality worldwide. Tumor necrosis factor-alpha (TNF-α) is a powerful proinflammatory cytokine involved in the pathogenesis of AECOPD. Therefore, we proposed a close correlation between the TNF-α polymorphism [-308G/A (rs1800629), +489G/A (rs1800610)] and the disease progress of patients with AECOPD. Comparison of the TNF-α genoty ...[more]

PMID: 33748274

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Project description:AimTo evaluate the association between the tumour necrosis factor alpha-308 (TNF-α-308) gene polymorphism and the risk of digestive system cancers.MethodsAll eligible case-control studies published up to December 2012 were identified by searching PubMed, Web of Science, Embase and China National Knowledge Internet without language restrictions. The risk of digestive system cancers associated with the TNF-α-308 polymorphism was estimated for each study using odds ratio (OR) together with its 95%CI, respectively. Cochrane Collaboration RevMan 5.1 was used to perform the analysis. A χ²-test-based Q statistic test and an I² test were performed to assess the between-study heterogeneity. When the Q test was significant (P < 0.05) or I² > 50%, the random effects model was used, otherwise the fixed effects model was used.ResultsFifty-eight studies from fifty-five publications with a total of 9986 cancer patients and 15511 healthy controls were included. Overall, a significant association was found between the TNF-α-308 polymorphism and the risk of digestive system cancers [dominant model: OR = 1.23, 95%CI: 1.09-1.39, (G/A) vs (G/G): OR = 1.15, 95%CI: 1.02-1.28, (A/A) vs (G/G): OR = 1.44, 95%CI: 1.19-1.73, recessive model: OR = 1.38, 95%CI: 1.15-1.66]. Furthermore, when the analysis was stratified by ethnicity, similar results were observed in both the Asian and Caucasian populations, except for the dominant model and heterozygote comparisons in the Asian population [dominant model: OR = 1.24, 95%CI: 0.99-1.56, (G/A) vs (G/G): OR = 1.09, 95%CI: 0.96-1.24]. When the cancer type subgroups were examined, similar results were detected in gastric and hepatocellular carcinomas; however, no significant association was observed among other digestive system cancers.ConclusionThe TNF-α-308 gene polymorphism may be significantly associated with the risk of gastric and hepatocellular carcinomas, but not colorectal, pancreatic, or oesophageal cancer, in the Asian population.

Project description:Background and objectiveThe association between TNF-α -308 G/A polymorphism and COPD remains controversial due to insufficiently strict study designs and small group sizes among different studies. In the present study, a meta-analysis update which followed a stricter procedure was performed to obtain a clearer understanding of this association.MethodsA comprehensive database search was conducted to identify the case-control studies published up to July 2015 which reported an association between the TNF-α -308 G/A polymorphism and COPD risk. Data were extracted to calculate pooled odds ratios with 95% confidence intervals under the most appropriate genetic and allelic models. Sensitivity was analyzed, and heterogeneity as well as publication bias was assessed.ResultsThirty-eight eligible studies, comprising 3,951 COPD cases and 5,110 controls, were included in this study, among which 22 studies comprising 2,067 COPD cases and 2,167 controls were performed in Asians, and 16 studies comprising 1,884 COPD cases and 2,943 controls were in non-Asians. The overall result showed that TNF-α -308 G/A polymorphisms were significantly associated with increased COPD risk in both the codominant genetic and allelic models. Individuals with the GA or AA genotype were more susceptible to COPD development than those with the GG genotype. In addition, individuals with the AA genotype were more susceptible to developing COPD than those with the GA genotype. The subgroup analysis stratified by ethnicity supported the results in Asians but not in non-Asians. However, no association was found between TNF-α -308 G/A polymorphisms and COPD susceptibility either in Asians or in non-Asians in the meta-analysis conducted with restriction to former/current smokers.ConclusionThe present meta-analysis suggested that the TNF-α -308 G/A polymorphism was associated with an increased risk of COPD among Asians but not in non-Asians. Furthermore, individuals with the AA genotype of TNF-α -308 were more susceptible to developing COPD.

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Correlation between TNF-α -308 and +489 Gene Polymorphism and Acute Exacerbation of Chronic Obstructive Pulmonary Diseases.

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Correlation between TNF-<i>α</i> -308 and +489 Gene Polymorphism and Acute Exacerbation of Chronic Obstructive Pulmonary Diseases.

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