Association of IL-4 and IL-10 Polymorphisms With Preterm Birth Susceptibility: A Systematic Review and Meta-Analysis

Objective: 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. Methods: 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. Results: 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 vs. AG revealed significant association between IL-10-1082A/G (rs1800896) and PTB (OR [95% CI] = 0.87 [0.76, 0.99], p = 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) p-value. Eggers's publication bias plot and heterogeneity test (I-2 < 50%, p = 0.05) of IL-10-1082A/G (rs1800896) suggested that the funnel asymmetry could be due to publication bias rather than heterogeneity. Conclusion: The current study suggests that the over-dominant gene model AA + GG vs. 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.