• Hongxiang Lu, Dalin Wen, Xu Wang, Lebin Gan, Juan Du, Jianhui Sun, Ling Zeng, Jianxin Jiang, and Anqiang Zhang.
• State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University, Changjiang Branch Road 10, Daping Street, Yuzhong District, Chongqing, 400042, China.
• Crit Care. 2019 Jan 25; 23 (1): 26.

BackgroundPublished data revealed that host genetic variants have a substantial influence on sepsis susceptibility. However, the results have been inconsistent. We aimed to systematically review the published studies and quantitatively evaluate the effects of these variants on the risk of sepsis.MethodsWe searched the PubMed, EMBASE, Medline, Web of Knowledge, and HuGE databases to identify studies that investigated the associations between genetic variants and sepsis risk. Then, we conducted meta-analyses of the associations for genetic variants with at least three study populations and applied the Venice criteria to assess the association result credibility.ResultsA literature search identified 349 eligible articles that investigated 405 variants of 172 distinct genes. We performed 204 primary and 185 subgroup meta-analyses for 76 variants of 44 genes. The results showed that 29 variants of 23 genes were significantly associated with the risk of sepsis, including 8 variants of pattern recognition receptors (PRRs), 14 variants of cytokines, one variant of an immune-related gene and 6 variants of other genes. Furthermore, the cumulative epidemiological evidence of a significant association between each variant and the risk of sepsis was classified as strong or moderate for 18 variants. For the 329 variants with fewer than three study populations, 63 variants of 48 genes have been reported to be significantly associated with the risk of sepsis in a systematic review.ConclusionWe identified several genetic variants that could influence the susceptibility to sepsis by systematic review and meta-analysis. This study provides a comprehensive overview of the genetic architecture of variants involved in sepsis susceptibility and novel insight that may affect personalized targeted treatment in the future clinical management of sepsis.

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