Obstetrics and Gynecology Hospital of Fudan University, School of Medicine, Shanghai, China.
Institute of Reproduction and Development, Fudan University, Shanghai, China.
Front Immunol. 2022 Jul 4;13:917383. doi: 10.3389/fimmu.2022.917383. eCollection 2022.
Preterm birth (PTB) is a typical inflammatory disease with unclear pathogenesis. The studies investigating the relationship between anti-inflammatory factors IL-4 and IL-10 gene polymorphisms and PTB produced conflicting results. This systematic review and meta-analysis aimed to summarize the effects of IL-4 and IL-10 gene polymorphisms and clarify their possible association with PTB.
A systematic literature review was conducted using PubMed, Web of Science, and Cochrane library (up to 02 April 2022). The MeSH terms, related entry terms, and other names in "Gene" database were used to find relevant articles. A fixed- or random-effects model was used to calculate the significance of IL-4 and IL-10 gene polymorphisms, depending on study heterogeneity. The odds ratios (OR) and 95% confidence intervals (CIs) were calculated in the allele, recessive, dominant, co-dominant, and over-dominant models. The Eggers publication bias plot was used to graphically represent the publication bias.
Polymorphisms in two interleukins (IL-4-590C/T (rs2243250) = 5 and IL-10-592A/C (rs1800872), -819T/C (rs1800871) and -1082A/G (rs1800896) = 16) were found in 21 articles. Overall, only the over-dominant gene model AA + GG . AG revealed significant association between IL-10-1082A/G (rs1800896) and PTB (OR [95% CI] = 0.87 [0.76, 0.99], = 0.04). However, in the allele model, recessive model, dominant model, co-dominant model, and over-dominant model, the polymorphisms for IL-4-590C/T (rs2243250), IL-10-592A/C (rs1800872), and IL-10-819T/C (rs1800871) were not found to be associated with the risk of PTB. In gene models, no statistically significant association was found between IL-4-590C/T (rs2243250), IL-10-592A/C (rs1800872), IL-10-819T/C (rs1800871), and IL-10-1082A/G (rs1800896) polymorphisms and PTB in subgroup analyses by racial or control group Hardy-Weinberg Equilibrium (HWE) -value. Eggers's publication bias plot and heterogeneity test (I<50%, = 0.05) of IL-10-1082A/G (rs1800896) suggested that the funnel asymmetry could be due to publication bias rather than heterogeneity.
The current study suggests that the over-dominant gene model AA + GG . AG of IL-10-1082A/G (rs1800896) polymorphism may be associated with genetic susceptibility to PTB and may have a protective function against PTB risk. There was unclear association found between IL-4-590C/T (rs2243250), IL-10-592A/C (rs1800872) and IL-10-819T/C (rs1800871) polymorphisms and PTB. Due to the limitations of included studies and the risk of publication bias, additional research is required to confirm our findings.
https://inplasy.com/inplasy-2022-4-0044, identifier INPLASY202240044.
早产（PTB）是一种典型的炎症性疾病，其发病机制尚不清楚。研究探讨了抗炎因子 IL-4 和 IL-10 基因多态性与 PTB 之间的关系，但其结果存在争议。本系统评价和荟萃分析旨在总结 IL-4 和 IL-10 基因多态性的影响，并阐明其与 PTB 之间可能的关联。
使用 PubMed、Web of Science 和 Cochrane 图书馆（截至 2022 年 4 月 2 日）进行系统文献检索。使用“Gene”数据库中的 MeSH 术语、相关条目术语和其他名称来查找相关文章。根据研究异质性，使用固定或随机效应模型计算 IL-4 和 IL-10 基因多态性的显著性。在等位基因、隐性、显性、共显性和超显性模型中计算优势比（OR）和 95%置信区间（CI）。使用 Eggers 出版偏倚图以图形方式表示出版偏倚。
在 21 篇文章中发现了两种白细胞介素（IL-4-590C/T（rs2243250）= 5 和 IL-10-592A/C（rs1800872）、-819T/C（rs1800871）和-1082A/G（rs1800896）= 16）的多态性。总体而言，仅在 IL-10-1082A/G（rs1800896）的超显性基因模型 AA+GG. AG 中发现与 PTB 之间存在显著关联（OR[95%CI] = 0.87[0.76, 0.99]， = 0.04）。然而，在等位基因模型、隐性模型、显性模型、共显性模型和超显性模型中，IL-4-590C/T（rs2243250）、IL-10-592A/C（rs1800872）和 IL-10-819T/C（rs1800871）的多态性与 PTB 风险无关。在基因模型中，未发现 IL-4-590C/T（rs2243250）、IL-10-592A/C（rs1800872）、IL-10-819T/C（rs1800871）和 IL-10-1082A/G（rs1800896）多态性与 PTB 之间存在统计学显著关联。按种族或对照组 Hardy-Weinberg 平衡（HWE）-值进行亚组分析时，未发现 IL-4-590C/T（rs2243250）、IL-10-592A/C（rs1800872）、IL-10-819T/C（rs1800871）和 IL-10-1082A/G（rs1800896）多态性与 PTB 之间存在关联。Eggers 出版偏倚图和异质性检验（I<50%， = 0.05）表明，IL-10-1082A/G（rs1800896）的漏斗不对称可能是由于出版偏倚而不是异质性所致。
本研究表明，IL-10-1082A/G（rs1800896）多态性的超显性基因模型 AA+GG. AG 可能与 PTB 的遗传易感性相关，并可能对 PTB 风险具有保护作用。IL-4-590C/T（rs2243250）、IL-10-592A/C（rs1800872）和 IL-10-819T/C（rs1800871）多态性与 PTB 之间的关联尚不清楚。由于纳入研究的局限性和出版偏倚的风险，需要进一步的研究来证实我们的发现。
https://inplasy.com/inplasy-2022-4-0044，标识符 INPLASY202240044。
