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  • Title: Identification of interleukin-6 promoter polymorphisms in the Chinese Han population and their functional significance.
    Author: Gu W, Du DY, Huang J, Zhang LY, Liu Q, Zhu PF, Wang ZG, Jiang JX.
    Journal: Crit Care Med; 2008 May; 36(5):1437-43. PubMed ID: 18434913.
    Abstract:
    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. DESIGN: Genetic, functional, and association studies. SETTING: National key laboratory of trauma and departments of traumatic surgery in two teaching hospitals. SUBJECTS: A total of 348 healthy blood donors and 105 patients with major trauma. INTERVENTIONS: None. MEASUREMENTS AND MAIN 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.
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