Shao Yiming, Li Jia, Cai Yujie, Xie Yuliu, Ma Guoda, Li You, Chen Yanyan, Liu Gen, Zhao Bin, Cui Lili, Li Keshen
Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, 57 Renmin Avenue, Xiashan District, Zhanjiang 524001, China ; Intensive Care Unit, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Intensive Care Unit, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Mediators Inflamm. 2014;2014:916202. doi: 10.1155/2014/916202. Epub 2014 Feb 20.
MicroRNA-146a (miR-146a) acts as a pivotal regulatory molecule in immune response and various diseases, such as carcinoma and autoimmune diseases. Growing evidences have demonstrated the association of miR-146a gene single-nucleotide polymorphisms (SNPs) with risk of several diseases, but no genetic relevance studies of miR-146a gene polymorphisms to sepsis have been reported by now. Our study has analyzed the association of sepsis with two functional miR-146a gene SNPs rs2910164 G/C and rs57095329 A/G in a Chinese Han population (226 sepsis cases; 206 healthy controls). Our results indicated a higher prevalence of the miR-146a gene SNP rs2910164 C allele and CC genotype in patients with severe sepsis (rs2910164G versus rs2910164C: P = 0.0029, odds ratio (OR) = 1.664; GG+GC versus CC: P = 0.0045, OR = 1.947). Neither the genotype nor the allele in rs57095329 showed significant differences between the septic cases and the controls (P = 0.5901 and 0.3580, resp.), and no significant difference was observed in the subgroups. In addition, we confirmed that the two SNPs rs2910164 and rs57095329 could functionally affect the miR-146a expression levels and the reduction of miR146a was accompanied with the upregulation of the expression levels of TRAF-6 and IRAK-1 in severe sepsis patients. This present study might provide valuable clinical evidence that miR-146a gene polymorphism rs2910164 is associated with the risk of severe sepsis.
微小RNA-146a（miR-146a）在免疫反应及多种疾病（如癌症和自身免疫性疾病）中发挥关键调节分子的作用。越来越多的证据表明，miR-146a基因单核苷酸多态性（SNP）与多种疾病的风险相关，但目前尚无关于miR-146a基因多态性与脓毒症遗传相关性的研究报道。我们的研究分析了中国汉族人群（226例脓毒症患者；206例健康对照）中脓毒症与两个功能性miR-146a基因SNP rs2910164 G/C和rs57095329 A/G的相关性。我们的结果表明，严重脓毒症患者中miR-146a基因SNP rs2910164 C等位基因和CC基因型的患病率更高（rs2910164G与rs2910164C：P = 0.0029，比值比（OR）= 1.664；GG + GC与CC：P = 0.0045，OR = 1.947）。rs57095329的基因型和等位基因在脓毒症病例与对照组之间均未显示出显著差异（分别为P = 0.5901和0.3580），在亚组中也未观察到显著差异。此外，我们证实这两个SNP rs2910164和rs57095329可在功能上影响miR-146a的表达水平，在严重脓毒症患者中，miR146a的降低伴随着TRAF-6和IRAK-1表达水平的上调。本研究可能提供有价值的临床证据，表明miR-146a基因多态性rs2910164与严重脓毒症的风险相关。
