Abstract

Abstract Background Great diversity among public hereditary variants may play a role in the susceptibility and severity of acute rheumatic fever (ARF)/rheumatic heart disease (RHD). Cytokine gene polymorphisms may contribute to the disease-associated cytokine imbalance. However, to the best of our knowledge, there is no existing meta-analysis concerning an association of the cytokine gene functional polymorphisms with the susceptibility / severity of ARF/RHD. Aims To investigate the potential association between cytokine gene functional polymorphisms of TNF-α, TGF-β, IL-10, IL-6 and IL-1β and the susceptibility and severity of ARF/RHD. Methods Comprehensive and structured search on Pubmed/Medline, Embase, EBSCO, and Cochrane Central Register of Controlled Trials was performed. Statistical analyses were performed using STATA. First, we performed direct pairwise meta-analysis. Then, a network meta-analysis was performed with the consistency model to compare the genetic models of different cytokine gene polymorphisms. Results Evidence derived from the meta-analysis of 24 retrospective cohort and case-control studies identified that elevated serum levels of TNF-α have been observed in ARF cases, occurring as a result of a SNP (-308G>A) in the promoter site of the TNF-α gene. Our results also suggest that IL-1β (-511) C/T polymorphism, TGF-β1 [rs1800469], and IL-1β [rs2853550] single nucleotide polymorphisms (SNPs) contributed to the susceptibility of ARF/RHD. Egger’s test did not demonstrate significant asymmetry in the dominant. Conclusion In summary, the polymorphism model increased the risk of RHD in the dominant genetic model, recessive genetic model, homozygote model and allelic genetic model among non-Asians while, recessive genetic model and homozygote model among Asians.

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