The association of polymorphisms of TLR4 and CD14 genes with susceptibility to sepsis in a Chinese population.
BACKGROUND
Sepsis is now the leading cause of death in the non-cardiovascular intensive care unit (ICU). Recent research suggests that sepsis is likely to be due to an interaction between genetic and environmental factors. Genetic mutations of toll-like receptor 4 (TLR4) and cluster of differentiation 14 (CD14) genes are involved in the immune and (or) inflammatory response. These may contribute to the susceptibility to sepsis in patients. This study was designed to evaluate whether the TLR4 and cluster CD14 gene polymorphisms are associated with susceptibility to sepsis.


METHODS
The single nucleotide polymorphisms (SNPs) of TLR4 (rs10759932, rs11536889, rs7873784, rs12377632, rs1927907, rs1153879) and CD14 (rs2569190 and rs2563298) in patients with sepsis and control subjects in the Guangxi Province were analyzed by using the polymerase chain reaction-single base extension (PCR-SBE) and DNA sequencing methods.


RESULTS
The rs11536889 polymorphism in TLR4 and rs2563298 polymorphism in CD14 were significantly associated with the risk of sepsis when compared to the control group. The frequencies of rs11536889 and rs2563298 polymorphisms in the group with sepsis were higher than that in the control group (OR = 1.430, 95% CI, 1.032-1.981, P<0.05; OR = 2.454, 95% CI, 1.458-4.130, P<0.05, respectively). Followed up haplotype analysis suggested that there were two haplotypes in which increased risk factors for sepsis were indicated.


CONCLUSIONS
The rs11536889 polymorphism in TLR4 and rs2563298 polymorphism in CD14, and two haplotypes were associated with increased susceptibility to sepsis.
Intensive Care Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, No.18 Zhongshan Road II, Baise, 533099, Guangxi, PR China. whycoolkl@163.com.
Haiyan
H
Wang
Intensive Care Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, No.18 Zhongshan Road II, Baise, 533099, Guangxi, PR China. wysh22@163.com.
Yesheng
Y
Wei
Intensive Care Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, No.18 Zhongshan Road II, Baise, 533099, Guangxi, PR China. zengyirr@163.com.
Yi
Y
Zeng
Intensive Care Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, No.18 Zhongshan Road II, Baise, 533099, Guangxi, PR China. gxbsqyq@126.com.
Yueqiu
Y
Qin
Intensive Care Unit, the People's Hospital of Guangxi Zhuang Autonomous Region, 6 Taoyuan Road, Nanning, 530021, Guangxi, PR China. icuxiong@sina.com.
Bin
B
Xiong
Intensive Care Unit, Minzu Hospital of Guangxi Zhuang Autonomous Region, 323 Mingxiu East Road, Nanning, 530021, Guangxi, PR China. icuqg@aliyun.com.
Gang
G
Qin
Intensive Care Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, No.18 Zhongshan Road II, Baise, 533099, Guangxi, PR China. ttgxlj@163.com.
Jun
J
Li
Intensive Care Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, No.18 Zhongshan Road II, Baise, 533099, Guangxi, PR China. syhdh-007@163.com.
Donghai
D
Hu
Intensive Care Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, No.18 Zhongshan Road II, Baise, 533099, Guangxi, PR China. qqshown@163.com.
Xiaowen
X
Qiu
Department of Surgery and Cancer, Imperial College London, Chelsea and Westminster Hospital, London, SW10 9NH, UK. s.sooranna@imperial.ac.uk.
Suren R
SR
Sooranna
Intensive Care Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, No.18 Zhongshan Road II, Baise, 533099, Guangxi, PR China. liaopinhu@163.com.
Liao
L
Pinhu
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018805:Sepsis / Q000235:genetics*; D017422:Sequence Analysis, DNA; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D055815:Young Adult
D018950:Lipopolysaccharide Receptors; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4