ABSTRACT

Background

Molecular epidemiological studies have sought associations between interleukin-6 (IL-6) polymorphisms and the risk of systemic lupus erythematosus (SLE); however, the results are controversial. Therefore, we conducted a meta-analysis with trial sequential analysis to evaluate a more accurate estimation of the associations.

Methods

Published literatures reporting the relationships of two IL-6 polymorphisms (G-174C and G-572C) and SLE risk were retrieved from electronic databases such as PubMed and EMBASE. The most appropriate genetic model was chosen for each polymorphism. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Trial sequential analysis (TSA) was introduced to assess the information size and the positive results.

Results

With 17 studies (2780 cases and 3100 controls) included, a dominant association (CC+GC vs. GG) was suggested for G-174C polymorphism, and compared with the GG genotype, the CC+GC genotype of G-174C was associated with a decreased SLE risk (OR = 0.71; 95% CI = 0.56–0.88, P =.02). No association was found for G-572C under all genetic models (e.g. OR and 95%CI for CC+GC vs. GG: 0.89, 0.73–1.08, P =.22). Subgroup analyses indicated that SLE risk decreased in G-174C polymorphism by subgroups of Caucasian population, publications after 2010, studies with high quality, and studies complied with Hardy–Weinberg equilibrium (HWE). TSA suggested that the sample sizes used for G-572C were insufficient.

Conclusion

We found that the minor allele C of IL6G-174C polymorphism is a protective factor in SLE. Further studies with a larger sample size are needed to confirm the null association for G-572C.

中文翻译：

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Interleukin-6 基因多态性与系统性红斑狼疮风险之间的关联：具有试验顺序分析的 Meta 分析。

摘要

背景

分子流行病学研究已经探索了白细胞介素 6 (IL-6) 多态性与系统性红斑狼疮 (SLE) 风险之间的关联；然而，结果是有争议的。因此，我们通过试验序贯分析进行了荟萃分析，以评估更准确的关联估计。

方法

从 PubMed 和 EMBASE 等电子数据库中检索报告了两种 IL-6 多态性（G-174C 和 G-572C）与 SLE 风险关系的已发表文献。为每个多态性选择最合适的遗传模型。计算比值比 (OR) 和 95% 置信区间 (CI)。引入试验序贯分析（TSA）来评估信息量和阳性结果。

结果

纳入 17 项研究（2780 例病例和 3100 例对照），表明 G-174C 多态性存在显性关联（CC+GC 与 GG），与 GG 基因型相比，G-174C 的 CC+GC 基因型与SLE 风险降低（OR = 0.71；95% CI = 0.56–0.88，P =.02）。在所有遗传模型下均未发现 G-572C 的关联（例如，CC+GC 与 GG 的 OR 和 95%CI：0.89、0.73–1.08，P =.22）。亚组分析表明，高加索人群亚组、2010 年之后的出版物、高质量研究和符合哈代-温伯格平衡 (HWE) 的研究，SLE 风险在 G-174C 多态性方面降低。TSA 建议用于 G-572C 的样本量不足。

结论

我们发现 IL6G-174C 多态性的次要等位基因 C 是 SLE 的保护因素。需要更大样本量的进一步研究来确认 G-572C 的无效关联。