Clinical relevance of single nucleotide polymorphisms in the CXCL1 and CXCL12 genes in patients with major trauma

Background Genetic backgrounds have been recognized as significant determinants of susceptibility to sepsis. CXC chemokines play a significant role in innate immunity against infectious diseases. Genetic polymorphisms of CXC chemokine genes have been widely studied in inflammatory and infectious diseases but not in sepsis. Thus, we aimed to investigate the clinical relevance of CXC chemokine gene polymorphisms and susceptibility to sepsis in a traumatically injured population. Methods Thirteen tag single nucleotide polymorphisms (tSNPs) were selected from CXC chemokine genes using a multi-marker tagging algorithm in the Tagger software. Three independent cohorts of injured patients (n = 1700) were prospectively recruited. Selected SNPs were genotyped using an improved multiplex ligation detection reaction (iMLDR) method. Cytokine production in LPS-stimulated whole blood was measured using an enzyme-linked immunosorbent assay. Results Among the 13 tSNPs, four SNPs (rs1429638, rs266087, rs2297630 and rs2839693) were significantly associated with the susceptibility to sepsis, and three (rs3117604, rs1429638 and rs4074) were significantly associated with an increased multiple organ dysfunction score (MODS score) in the derivation cohort. However, only the clinical relevance of rs1429638 and rs266087 was confirmed in the validation cohorts. In addition, rs2297630 was significantly associated with IL-6 production. Conclusions The rs1429638 polymorphism in the CXCL1 gene and the rs2297630 polymorphism in the CXCL12 gene were associated with altered susceptibility to sepsis, and might be used as important genetic markers to assess the risks of sepsis in trauma patients. Level of Evidence Prognostic and epidemiologic study, level II. Corresponding Author: Ling Zeng, MD or Jian-Xin Jiang, MD, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China Phone/fax: +86-023-687757401. E-mail: yswang77@126.com or jjxcqing@126.com Conflicts of interest: All authors report no conflicts of interest Funding: Supported by the National Natural Science Foundation of China (81571892 and 81660317), National Key Technology Program (2012BAI11B01). © 2018 Lippincott Williams & Wilkins, Inc.

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