Genetic variants of microRNA sequences and susceptibility to sepsis in patients with major blunt trauma.
Genetic variants of microRNA sequences and susceptibility to sepsis in patients with major blunt trauma.
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DOI：
10.1097/sla.0000000000000687
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发表时间：
2015
影响因子：
9
通讯作者：
Anqiang Zhang;W. Gu;L. Zeng;lianyang zhang;D. Du;Mao Zhang;J. Hao;Cai-li Yue;Jian-xin Jiang
中科院分区：
文献类型：
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作者：
Anqiang Zhang;W. Gu;L. Zeng;lianyang zhang;D. Du;Mao Zhang;J. Hao;Cai-li Yue;Jian-xin Jiang
目的系统调查常见前体microRNA（pre-miRNA）单核苷酸多态性（SNP），并评价其在严重钝性创伤患者中的临床意义。背景最近的证据表明，小的非编码RNA分子（称为miRNA）可以作为重要的负性基因调节因子发挥作用，并与各种疾病的发病机制有关。方法我们进行了一项2阶段研究，以检查9个选择的SNPs与脓毒症易感性的影响，在中国的1268例创伤患者（1个筛选队列，n = 666）和2个独立验证队列（分别为n = 286和n = 316）。结果在9个具有潜在功能意义的SNPs中，只有1个（miR-608 rs 4919510）在所有3个独立研究队列中与脓毒症和多器官功能障碍的高风险密切相关。当将这3个研究队列组合在一起时，观察到rs 4919510多态性的更强关联。此外，rs 4919510多态性与促炎性细胞因子的较高产生和抗炎性细胞因子的较低产生显著相关。体外实验进一步表明，该多态性的G→C变体可显著增加成熟miR-608的表达。结论hsa-mir-608中rs 4919510 G/C SNP可能是严重创伤患者脓毒症的预后生物标志物。进一步表征miRNA SNPs可能为研究脓毒症和开发新的治疗方法开辟新的途径。
OBJECTIVE The objective of this study was to conduct a systematic survey of common precursor microRNA (pre-miRNA) single nucleotide polymorphisms (SNPs) and evaluate their clinical relevance in patients with major blunt trauma. BACKGROUND Recent evidence indicates that small noncoding RNA molecules known as miRNAs can function as important negative gene regulators and are implicated in the pathogenesis of various diseases. METHODS We conducted a 2-stage study to examine the impact of 9 selected SNPs with potential functional significance on the susceptibility to sepsis of 1268 trauma patients (1 screening cohort, n = 666) and 2 independent validated cohorts (n = 286 and n = 316, respectively) in China. RESULTS Among the 9 selected SNPs with potential functional significance, only 1 (miR-608 rs4919510) was found to be strongly associated with a higher risk of developing sepsis and multiple organ dysfunction in all 3 independent study cohorts. An even stronger association was observed for the rs4919510 polymorphism when combining these 3 study cohorts together. In addition, the rs4919510 polymorphism showed a significant correlation with a higher production of proinflammatory cytokines and a lower production of anti-inflammatory cytokines. In vitro experiments further indicated that the G→C variant of this polymorphism could significantly increase the expression of mature miR-608. CONCLUSIONS Our results indicate that the rs4919510G/C SNP in hsa-mir-608 may be a prognostic biomarker for sepsis in patients with major trauma. Further characterization of miRNA SNPs may open new avenues for studying sepsis and developing novel therapeutic approaches.