Association between rs1800629 polymorphism in tumor necrosis factor-α gene and dilated cardiomyopathy susceptibility: Evidence from case-control studies

Abstract

Objective: Several published studies have investigated the association between the -308G/A (rs1800629) polymorphism in the tumor necrosis factor-α (TNF-α) gene and the risk of dilated cardiomyopathy (DCM). However, the TNF-α gene polymorphism has a controversial role in the pathogenesis of DCM among different populations. In the present study, a meta-analysis was performed to resolve this inconsistency.

Methods: Potentially eligible papers reporting an association between the TNF-α rs1800629 polymorphism and DCM susceptibility were searched in 4 databases including PubMed, EMBASE, Chinese Biomedical Database (CBM), and the Cochrane Library up to April 1, 2018. The odds ratio (OR) with its 95% confidence interval (CI) was used to estimate the strength of the associations. Subgroup analysis based on the ethnicity, studies with or without ischemic and valvular DCM was conducted. Publication bias detection was conducted using Begg test.

Results: Nine papers detailing case-control studies were included, reporting a total of 1339 DCM cases and 1677 healthy controls. The meta-analysis results indicated that TNF-α rs1800629 was associated with increased DCM susceptibility in the populations studied under the heterozygous model (AG vs GG: OR = 1.91, 95% CI = 1.05-3.50, P = .035) and dominant model (AG + AA vs GG: OR = 1.87, 95% CI = 1.01-3.45, P = .046). In the subgroup analysis for ethnicity, rs1800629 polymorphism was significantly associated with the susceptibility of DCM for Asians under the 5 models (A vs G: OR = 2.87, 95% CI = 1.56-5.30, P = .001; AA vs GG: OR = 3.95, 95% CI = 1.13-13.82, P = 0.031; AG vs GG: OR = 3.8, 95% CI = 1.57-9.19, P = .003; AA vs GG + AG: OR = 2.51, 95% CI = 1.41-4.49, P = .002; AG + AA vs GG: OR = 3.77, 95% CI = 1.54-9.20, P = .004).

Conclusion: There may be a moderate association between TNF-α rs1800629 polymorphism and DCM susceptibility in the whole populations studied; however, TNF-α rs1800629 polymorphism was significantly associated with the susceptibility of DCM for Asians, which indicates that such associations may be different between ethnicities.

Figure 1

chart of the study selection process.

Figure 2

The forest plot of the pooled ORs of the association of TNF-α rs1800629 with dilated cardiomyopathy susceptibility under the dominant model. OR = odds ratios, TNF-α = tumor necrosis factor-α.

Figure 3

Subgroup analysis by ethnicity between rs1800629 polymorphism and the susceptibility of DCM for Asians under homozygous model (A), allele model (B), dominant model (C), recessive model (D), and heterozygous model (E). DCM = dilated cardiomyopathy.

Figure 4

Publication bias under the dominant model.