The functional polymorphisms of miR-146a are associated with susceptibility to severe sepsis in the Chinese population.
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.
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.
Yiming
Y
Shao
Intensive Care Unit, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Jia
J
Li
Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, 57 Renmin Avenue, Xiashan District, Zhanjiang 524001, China.
Yujie
Y
Cai
Intensive Care Unit, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Yuliu
Y
Xie
Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, 57 Renmin Avenue, Xiashan District, Zhanjiang 524001, China.
Guoda
G
Ma
Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, 57 Renmin Avenue, Xiashan District, Zhanjiang 524001, China.
You
Y
Li
Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, 57 Renmin Avenue, Xiashan District, Zhanjiang 524001, China.
Yanyan
Y
Chen
Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, 57 Renmin Avenue, Xiashan District, Zhanjiang 524001, China.
Gen
G
Liu
Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, 57 Renmin Avenue, Xiashan District, Zhanjiang 524001, China.
Bin
B
Zhao
Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, 57 Renmin Avenue, Xiashan District, Zhanjiang 524001, China.
Lili
L
Cui
Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, 57 Renmin Avenue, Xiashan District, Zhanjiang 524001, China.
Keshen
K
Li
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002681:China; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D018805:Sepsis / Q000201:enzymology / Q000235:genetics*; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D048029:TNF Receptor-Associated Factor 6; C531552:TRAK1 protein, human