Abstract
Many genetic variations have been identified to associate with sepsis in numerous studies, but the function of these variants in influencing sepsis is a complex process. We make use of mate-analysis and other analytic strategies (eQTL analysis and PPI network) to investigate the effect of interleukin-10 (IL10) on sepsis. Single-nucleotide polymorphisms (SNPs) in IL10 were analyzed in 3011 septic cases and 2976 controls from 22 studies. In results, the IL10-rs1800871 showed a significant association with sepsis in Asians (P < 0.05). Moreover, there is a association between rs1800896 and sepsis in pooled populations and Asians (P < 0.05). However, there is no association between rs1800872 and sepsis in different models. The three polymorphisms were also identified for the regulation of IL10 expression in an eQTL analyze, and the increased IL10 expression was related to the development of sepsis. Furthermore, the IL10 was discovered to associate with the expression of DRD1, TANK, MKL1, and STARD3NL genes in another independent cohort, which are functionally enriched for IRF3 (interferon regulatory factor 3)/IRF7 (interferon regulatory factor 7) and hormone pathways. In conclusion, the study confirmed the association between IL10 polymorphisms (rs1800871, rs1800872, rs1800896) and sepsis, and suggested the role of the variants in inflammatory pathologies.
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