Circulating Inflammatory Mediators and Genetic Polymorphisms of Inflammation Mediators and Their Association with Factors Related to Abdominal Aortic Aneurysm: A Systemic Review and Meta-Analysis

Background: This study aimed to explore the levels of circulating inflammatory factors CRP, IL-6, IL-10 and TNF-alpha based on the literature review. This study also examined the influence of single nucleotide polymorphism (SNP) sites on the susceptibility of abdominal aortic aneurysm (AAA) using meta-analysis and intended to provide additional information on pathogenesis of AAA research. Methods: Electronic databases including PubMed and Web of Science were systemically searched to collect the information on AAA, inflammatory factors such as CRP, IL-6, IL-10, TNF-alpha and the SNP sites for data extraction. Altogether six SNPs in four genes (rs3091244, CRP; rs1800947, CRP; rs1205, CRP; rs1800795, IL-6; rs1800896, IL-10; and rs1800629, TNF) were assessed. Results: This study enrolled altogether 41 relevant investigations involving 9,007 AAA patients to carry out meta-analysis. According to pooled analysis, circulating CRP and IL-6 levels were shown to be related to the AAA, while plasma IL-10 and TNF-alpha levels were not associated with AAA. The circulating CRP level standard mean difference (SMD) was 0.30 (95% confidence interval (CI): 0.17-0.43), the IL-6 level SMD was 0.34 (95% CI: 0.20-0.49), the IL-10 level SMD was -0.01 (95% CI: -0.09-0.06), and the TNF-alpha level SMD was 0.09 (95% CI: 0.00- 0.19). Similarly, the odds ratio (OR) of rs3091244 (CRP) under the recessive gene model was 1.70 (95% CI: 1.13-2.57). In addition, individuals with A and T mutant genes at locus rs3091244 might have a higher tendency of AAA susceptibility than those with C allele. Consecutively, the OR was 0.91 (95% CI: 0.51-0.97) for rs1800795 (IL-6) locus in the allele model, and individuals with G mutant gene at locus rs1800795 (IL-6) might be less susceptible to AAA than those with C allele. Meanwhile, the rs1800896 (IL-10) locus had a positive association under the five statistical models, and individuals with A mutant gene at locus rs1800896 might have a higher susceptibility to AAA than those with G allele. Nevertheless, the rs1800947 (CRP), rs1205 (CRP), and rs1800629 (TNF) loci did not have positive correlation under the five statistical models, with no statistical significance. The results indicate that the gene polymorphisms at rs1800629, rs1800947, and rs1205 loci were not related to the AAA susceptibility. Conclusions: Gene polymorphisms in certain known inflammatory mediators related to AAA susceptibility might serve as potential predictive biomarkers for clinical applications. Moreover, SNP of inflammatory mediators relevant to abdominal aortic aneurysmal formation and progression need extensive investigations to confirm these results.

Automated summary

This study investigated the levels of circulating inflammatory factors and the influence of SNP sites on AAA susceptibility. The results showed associations of CRP and IL-6 levels with AAA, while IL-10 and TNF-alpha levels were not correlated. Gene polymorphisms may serve as potential predictive biomarkers for AAA susceptibility, with further investigations needed for confirmation.