Identification of interleukin-6 promoter polymorphisms in the Chinese Han population and their functional significance.
OBJECTIVE
Interleukin-6 (IL-6) is a pivotal cytokine in both innate and adaptive immunity. Several polymorphisms in the IL-6 promoter have been reported in Western populations. However, little is known about their occurrence in the Chinese population. The functionality of IL-6 promoter polymorphisms remains controversial.


METHODS
Genetic, functional, and association studies.


METHODS
National key laboratory of trauma and departments of traumatic surgery in two teaching hospitals.


METHODS
A total of 348 healthy blood donors and 105 patients with major trauma.


METHODS
None.


RESULTS
Identification of polymorphisms in the IL-6 promoter was performed using sequencing and restriction fragment length polymorphism methods. Their functionality was assessed by observation of transcription activity, IL-6 production, and their clinical relevance in 105 patients with major trauma. Only one variant (C-572G) was identified in IL-6 promoter in Chinese Han population. This polymorphism was associated with IL-6 production by peripheral leukocytes in response to ex vivo lipopolysaccharide stimulation in an allele-dose-dependent effect. The C-->G variation at position -572 could reduce transcriptional activity of the IL-6 promoter as shown in both U-937 and K562 cell lines. Moreover, the -572 polymorphism was associated with lower risk of sepsis in major trauma patients.


CONCLUSIONS
The -572 polymorphism, a unique variation in the IL-6 promoter in the Chinese Han population, may be used as a relevant risk estimate for sepsis in trauma patients.
Gu
Wei
W
State Key Laboratory of Trauma, Burns, and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Daping, Chongqing, China.
Du
Ding-yuan
DY
Huang
Jian
J
Zhang
Lian-yang
LY
Liu
Qin
Q
Zhu
Pei-fang
PF
Wang
Zheng-guo
ZG
Jiang
Jian-xin
JX
D000293:Adolescent; D000328:Adult; D002681:China; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018805:Sepsis / Q000209:etiology / Q000235:genetics*; D014947:Wounds and Injuries / Q000150:complications*
D015850:Interleukin-6