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The association between interleukin-6 gene -174G/C single nucleotide polymorphism and sepsis: an updated meta-analysis with trial sequential analysis.

ABSTRACT:

Background

This article intends to explore the association between interleukin-6 gene (IL-6) -174 G/C single nucleotide polymorphism (SNP) and the risk and mortality of sepsis by conducting this updated meta-analysis with trial sequential analysis.

Methods

References were made to PubMed, Web of Science, China National Knowledge Infrastructure for studies available by September 2018. Each publication was screened for its eligibility and data accessible. Statistical analysis was conducted on Stata 14.1 and TSA software 0.9.5.10 Beta RESULTS: Twenty studies (including 3282 cases and 4926 controls) and eight studies (including 610 cases and 1856 controls) were respectively enrolled in the analysis on the association between IL-6-174 G/C polymorphism and the risk and mortality of sepsis. The results did not present any association between IL-6-174 G/C polymorphism and the risk and mortality of sepsis. An exception was that IL-6-174 G/C polymorphism was correlated with worse outcome in non-adults in recessive model, co-dominant model (CC vs. GG) and allelic model, while trial sequential analysis revealed it could be a false positive result nevertheless.

Conclusions

IL-6-174 G/C polymorphism is not associated with the risk and mortality of sepsis. Trial sequential analysis showed that a large sample size was needed to get a more reliable result of the association between IL-6-174 G/C polymorphism and sepsis in non-adults.

SUBMITTER: Chen Y

PROVIDER: S-EPMC6379942 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Although numerous epidemiological studies have investigated the association between -174G/C(rs1800795) polymorphism in the interleukin-6 (IL-6) gene-stimulatory region and the risk of ischemic stroke (IS), they failed to reach a unified conclusion. The true relationship between -174G/C(rs1800795) polymorphism and IS remains controversial and unclear. Therefore, in this meta-analysis, we aimed to analyze more precisely the association between -174G/C(rs1800795) single-nucleotide polymorphism (SNP) of IL-6 gene and IS in a larger pooled population. Methods: A comprehensive literature search was performed in PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials until June 30, 2021. A fixed or random-effects model was utilized based on heterogeneity between studies. The odds ratios (ORs) and 95% confidence intervals (Cis) were calculated in the models of allele comparison (G vs. C), homozygote comparison (GG vs. CC) and (GC vs. CC), dominant (GG vs. GC + CC), hyper dominant (GG + CC vs. GC), and recessive (GG + GC vs. CC) to determine the strength of associations. Results: This meta-analysis included 13 case-control studies in 35 articles with 5,548 individuals. Overall, no significant associations between IL-6 -174G/C(rs1800795) and IS were identified (G vs. C:OR [95% CI] = 0.99 [0.81, 1.21], P = 0.91; GG + CC vs. GC:0.97 [0.85, 1.11], P = 0.66; GG vs. GC + CC: 1.01 [0.81, 1.25], P = 0.94; GC vs. CC: OR [95% CI] = 1.01 [0.68, 1.5], P = 0.96; GG vs. CC:0.93 [0.57, 1.51], P = 0.76; GG + GC vs. CC:0.97 [0.64, 1.47], P = 0.89). In the subgroup analyses by ethnicity or HWE P-value, there was a statistically significant association between IL-6 -174G/C(rs1800795) polymorphisms and IS in the alleles model; (G vs. C: LogOR [95% CI] = 0.14 [-0.16,.45], P = 0.00), homozygote model (GG vs. CC: LogOR [95% CI] = 0.18 [-0.58,.95], P = 0.00) and (GC vs. CC: LogOR [95% CI] = 0.2 [-0.46,.85], P = 0.00), dominant model (GG vs. GC + CC: OR [95% CI] = 0.02 [-0.72, 0.77], P = 0.00), and recessive model (GG + GC vs. CC: OR [95% CI]= -0.17 [-0.86,.52], P = 0.00) of the European population and in the dominant model (GG vs. GC + CC: OR [95% CI] = -0.13 [-0.51, 0.24]) of the Asian population. No statistical significance was identified in both six models of HWE p ≥ 0.2 group (both P ≥ 0.05). Conclusion: This meta-analysis revealed no correlation between IL-6 -174G/C(rs1800795) polymorphism and IS, whereas the subgroup analysis indicated that the relationship between IL-6 -174G/C(rs1800795) polymorphism and IS susceptibility varied significantly according to ethnicity and geography.