肿瘤坏死因子基因多态性与脓毒症易感性及预后间的关系

Study on the Relationships between Tumor Necrosis Factor Polymorphisms and Sepsis Susceptibility and Factor Productivity

目的:确定肿瘤坏死因子基因多态性与脓毒症易感性及细胞因子产量间的相关性。方法:采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)分析正常人群和脓毒症患者肿瘤坏死因子(TNF)-α启动子-308位点及TNF-β第一内含子+252位点基因的单碱基突变多态性之间的异同。采用双抗夹心酶联免疫吸附(ELISA)方法检测脓毒症患者血浆TNF-α和白细胞介素6(IL-6)的浓度。结果:45例脓毒症患者的TNFB2等位基因频率为67.78%,高于正常对照组的53.33%(P<0.05),TNFB2纯合子患者血浆TNF-α、IL-6浓度和病死率高于杂合子及TNFB1纯合子患者(P<0.05);而脓毒症组和对照组的TNF1和TNF2的基因频率差异无统计学意义(P>0.05),TNF1纯合子和TNF1/2杂合子之间的血浆TNF-α、IL-6浓度以及病死率的差异亦无统计学意义(P>0.05)。结论:TNF-β第一内含子+252位点的等位基因TNFB2与脓毒症的易感性和体内TNF-α、IL-6浓度有关。

Objective： To determine the relationship between the susceptibility of sepsis and the gene polymorphism of TNF. Methods： The single base change polymorphism in both TNF-α gene and TNF-β gene were analyzed in sepsis patients and normal controls by PCR-RFLP. TNF-α and IL-6 plasma concentrations were detected by enzyme-linked immunosorbent assay. Results： TNFB2 gene frequencies increased significantly in sepsis patients compared with those in controls（67.78%,53.33%,P 〈 0.05）. Higher TNF-α, IL-6 concentrations and mortality were found in TNFB2 homozygotes compared with those in TNFB1 homozygotes（P 〈 0.05）. No difference of allele frequencies or genotype distribution of TNF-α was noted between sepsis patients and controls（P 〉 0.05）. Conclusion： The TNFB2 allelic in the first intron of the TNF-β gene may be related to the susceptibility of sepsis and high concentrations of TNF-α and IL-6.