CD14基因多态性对严重烧伤后CD14表达的影响及其临床意义

The influence of CD14 genomic polymorphism on CD14 gene expression as well as protein release and its clinical significance in patients with extensive burns

目的探讨内毒素受体CD14C-159T基因多态性对烧伤后CD14合成与释放的影响及其与脓毒症易感性、患者预后的关系。方法26例烧伤面积大于30%的患者,采用聚合酶链反应及限制性内切酶HaeⅢ对PCR产物的消化作用检测CD14基因多态性。同时,对患者白细胞CD14、肿瘤坏死因子-α(TNF-α)mRNA表达,血清sCD14浓度与CD14-159位点基因型以及烧伤患者预后的关系进行了分析。结果TT、TC、CC三种基因型患者白细胞CD14 mRNA、TNF-αmRNA表达,血清sCD14浓度存在明显差异。其中TT、TC基因型CD14 mRNA表达均明显高于CC纯合子(P<0．05或P<0．01),伤后第7天CC基因型血浆sCD14水平显著低于TC基因型(P<0．05);同时,TT纯合子的TNF-αmRNA表达强度明显高于CC纯合子(P<0．05)。此外,伤后第7、21天死亡组CD14 mRNA表达量显著高于存活组(P<0．05)。结论CD14C-159T基因多态性可显著影响严重烧伤后CD14的合成与释放,并与烧伤患者脓毒症易感性有关,T等位基因可能是患者预后不良的高危基因标志物。

Objective To investigate the influence of a lipopolysaccharide receptor CD14-159C/T genomic polymorphism on CD14 gene expression as well as protein release, and the relation of sepsis susceptibility and prognosis in patients with extensive burns. Methods The study group consisted of 26 patients with burns covering more than 30% of the total body surface area. The CD14 gene polymorphism was determined by polymerase chain reaction （PCR） and subsequent HaeIII restriction enzyme digestion of the PCR products. Meanwhile, the association of CD14, TNF-α mRNA expression in leukocytes and soluble CD14 （sCD14） levels in serum with CD14-159 polymorphism as well as prognosis after burns was also studied. Results The T allele frequencies in sepsis patients and non-survivors were higher than those in non-septic patients and survivors. The levels of CD14 mRNA, TNF-α mRNA expression and serum sCD14 were significantly different among patient groups with CD14, TC, anti CC genotypes. The above differences were also existed between survivors and non-survivors. CD14 mRNA expression was higher in heterozygotes （TY and TC） than in C homozygous patients （P 〈 0. 05 or P 〈 0. 01 ）, and sCD14 level was higher in beterozygotes （TC） than C homozygous patients on day 7 posthurn （P 〈 0. 05 ）. During the 28-day observation period, mean TNF-α mRNA expression was higher in patients homozygous for T allele than C homozygotes （P 〈 0. 05 ）. In addition, higher CD14 mRNA values were found in non-survivors compared to those in survivors on days 7 and 28 posthurn （ P 〈 0. 05 ）. Conclusions CD14C-159T polymorphism might markedly influence CD14 mRNA expression and sCD14 levels, and it seems to be associated with sepsis susceptibility and prognosis in patients with extensive burns. The T allele could be a genetic risk marker of adverse prognosis.