一项综合荟萃分析，涵盖149项病例对照研究，以调查白细胞介素-6基因rs1800795多态性与多种疾病风险之间的关联。

A comprehensive meta-analysis comprising 149 case-control studies to investigate the association between IL-6 gene rs1800795 polymorphism and multiple disease risk.

作者信息

Harun-Or-Roshid Md, Mollah Md Nurul Haque

机构信息

Department of Statistics, University of Rajshahi, Rajshahi 6205, Bangladesh.

Department of Genetic Engineering & Biotechnology, University of Dhaka, Dhaka 1000, Bangladesh.

出版信息

Gene. 2023 Apr 20;861:147234. doi: 10.1016/j.gene.2023.147234. Epub 2023 Feb 1.

DOI:10.1016/j.gene.2023.147234

PMID:36736866

Abstract

BACKGROUND

Individual genome-wide association studies (GWAS) or single case-specific meta-analyses may not be sufficient evidence to take action against a specific gene function. Thus, we tried to determine a consensus association between the IL-6 gene rs1800795 polymorphism and multiple disease risks through an updated statistical meta-analysis.

METHOD

After systematically searching online databases, we found 149 case-control relevant datasets with a sample size of 96,153 (cases: 38,291 and controls: 57862) and conducted the meta-analysis using updated statistical models.

RESULTS

The analyses of this comprehensive meta-analysis revealed a significant association between IL-6 -174G/C polymorphism and overall disorder risk under all genetic models (C vs G: OR = 1.11, 95% CI = 1.08-1.13; p-value = 4.8E-17; CC vs GG: OR = 1.19, 95% CI = 1.13-1.26; p-value = 9.4E-12; CG vs GG: OR = 1.10, 95% CI = 1.06-1.14; p-value = 1.1E-07; CC + CG vs GG: OR = 1.13, 95% CI = 1.10-1.17; p-value = 1.1E-13; CC vs CG + GG: OR = 1.18, 95% CI = 1.06-1.31; p-value = 0.0019) and (OR > 1) with Asian ethnicity. The subgroup analyses based on the diseases revealed that the polymorphism was highly significantly increasing the risk of coronary artery disease (CAD) under all genetic models. Likewise, a significant association was observed with increased risk under three genetic models of inflammatory diseases (C vs G; CC vs GG; and CC vs CG + GG), and rheumatoid arthritis (C vs G; CG vs GG; and CC + CG vs GG). Conversely, the -174G/C SNP significantly decreased the risk of ischemic stroke under the two genetic models (C vs G; and CG vs GG). However, the other diseases included in this study showed no significant association with IL-6 (-174G/C) polymorphism.

CONCLUSION

This meta-analysis provided strong evidence for the association between IL-6 gene rs1800795 polymorphism and multiple disease risks. The IL-6 gene could be a useful prognostic biomarker for CAD, inflammatory disease, ischemic stroke, and rheumatoid arthritis.

摘要

背景

个体全基因组关联研究（GWAS）或单一病例特异性荟萃分析可能不足以作为针对特定基因功能采取行动的证据。因此，我们试图通过更新的统计荟萃分析来确定白细胞介素-6基因rs1800795多态性与多种疾病风险之间的共识关联。

方法

在系统检索在线数据库后，我们找到了149个病例对照相关数据集，样本量为96153（病例：38291例，对照：57862例），并使用更新的统计模型进行荟萃分析。

结果

这项综合荟萃分析的结果显示，在所有遗传模型下，白细胞介素-6 -174G/C多态性与总体疾病风险之间存在显著关联（C vs G：比值比=1.11，95%置信区间=1.08-1.13；p值=4.8×10-17；CC vs GG：比值比=1.19，95%置信区间=1.13-1.26；p值=9.4×10-12；CG vs GG：比值比=1.10，95%置信区间=1.06-1.14；p值=1.1×10-7；CC + CG vs GG：比值比=1.13，95%置信区间=1.10-1.17；p值=1.1×10-13；CC vs CG + GG：比值比=1.18，95%置信区间=1.06-1.31；p值=0.0019），且在亚洲种族中（比值比>1）。基于疾病的亚组分析表明，在所有遗传模型下，该多态性显著增加冠状动脉疾病（CAD）的风险。同样，在炎症性疾病的三种遗传模型（C vs G；CC vs GG；以及CC vs CG + GG）和类风湿性关节炎（C vs G；CG vs GG；以及CC + CG vs GG）下，观察到与风险增加存在显著关联。相反，在两种遗传模型（C vs G；以及CG vs GG）下，-174G/C单核苷酸多态性显著降低缺血性中风的风险。然而，本研究中纳入的其他疾病与白细胞介素-6（-174G/C）多态性无显著关联。