Functional significance of CD14 promoter polymorphisms and their clinical relevance in a Chinese Han population*

Abstract

OBJECTIVE: Several polymorphisms in the CD14 promoter have been reported to be associated with various inflammatory diseases. However, conflicting results have been shown in association studies in different populations. This study aimed to investigate the possible functional significance of both the G-1145A and T-159C polymorphisms in the CD14 promoter and their association with organ dysfunction and sepsis in adult trauma patients. DESIGN: Genetic, functional, and association studies. SETTING: National Key Laboratory of Trauma and Departments of Traumatic Surgery in two teaching hospitals. SUBJECTS: Three hundred twenty-five healthy volunteers and 105 patients with major trauma. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the five single nucleotide polymorphisms identified within CD14 promoter in a Chinese Han population, two single nucleotide polymorphisms (G-1145A and T-159C) were selected according to bioinformatics analysis. Promoter activity of polymorphisms was determined using the reporter gene assay. Plasma sCD14 and tumor necrosis factor-alpha levels were measured by enzyme-linked immunosorbent assay. Both single nucleotide polymorphisms significantly reduced transcriptional activity of the promoter, and were significantly associated with a decrease of inducible sCD14 and tumor necrosis factor-alpha production in an allele-dose effect. Moreover, trauma patients carrying the -1145 A or -159 C allele appeared to have a decreased risk of multiple organ dysfunction and sepsis. In addition, both polymorphisms had a marked synergistic effect. CONCLUSIONS: The CD14/-1145 and -159 polymorphisms are functional variants, which may function in a synergistic fashion, and could be used as biological risk predictors of multiorgan dysfunction and sepsis in trauma patients.