Clinical relevance of 13 cytokine gene polymorphisms in Chinese major trauma patients.
OBJECTIVE
To determine the clinical relevance of 13 reported common single-nucleotide polymorphisms (SNPs) of cytokine genes in patients with major trauma.


METHODS
Thirteen SNPs in nine key cytokine genes were selected for association study in 308 patients with major trauma on the basis of previous functional or association data. An allele-specific oligonucleotide array was developed and used to genotype 308 patients with major trauma. The clinical relevance of the 13 SNPs was assessed by observation of cytokine production and outcome of trauma patients.


RESULTS
Results from the allele-specific oligonucleotide array indicated that 8 [interleukin-1beta (IL-1beta)/-1470, IL-1beta/-511, IL-1beta/-31, IL-4/-589, IL-6/-572, IL-8/-251, IL-10/-819, and tumor necrosis factor alpha (TNFalpha)/-308] out of the 13 SNPs were associated with respective ex vivo cytokine production by peripheral leukocytes in response to lipopolysaccharide (LPS) stimulation at admission, or risk of development of sepsis or organ dysfunction in major trauma patients. Patients with more than four risk alleles of the eight SNPs had more than 50% sepsis morbidity and more severe organ dysfunction.


CONCLUSIONS
Polymorphisms of IL-1beta/-1470, IL-1beta/-511, IL-1beta/-31, IL-4/-589, IL-6/-572, IL-8/-251, IL-10/-819, and TNFalpha/-308 are susceptibility loci for the development of sepsis and organ dysfunction in major trauma patients.
Gu
Wei
W
State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Daping, Chongqing, 400042, China.
Zeng
Ling
L
Zhou
Jian
J
Jiang
Dong-po
DP
Zhang
Lianyang
L
Du
Ding-yuan
DY
Hu
Ping
P
Chen
Kehong
K
Liu
Qin
Q
Wang
Zheng-guo
ZG
Jiang
Jian-xin
JX
D000328:Adult; D044466:Asian People / Q000235:genetics*; D002681:China; D016207:Cytokines / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D009102:Multiple Organ Failure / Q000235:genetics*; D009104:Multiple Trauma / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018805:Sepsis / Q000235:genetics*; D015599:Trauma Severity Indices
D016207:Cytokines