肿瘤坏死因子基因多态性与多脏器功能障碍综合征的相关性研究  

A correlation study of tumor necrosis factor polymorphism and MODS

作　　者：窦琳[1] 曹书华[1] 刘娟[1] 王今达[1] 

机构地区：[1]天津市第一中心医院急救医学研究所ICU,300192

出　　处：《中华急诊医学杂志》2005年第5期408-412,共5页Chinese Journal of Emergency Medicine

基　　金：天津市卫生厅科研专项资金课题(12010402013)

摘　　要：目的探讨肿瘤坏死因子基因多态性与MODS易感性之间的相关性。方法采用聚合酶链式应-限制性片段长度多态性(polymerasechainreactionrestrictionfragmentlengthpolymorphism,PCR-RFLP)析正常人群和MODS患者TNF-α启动子-308位点及TNFβ第一内含子+252位点基因多态性之间的异同。采用ELISA方法检测MODS患者的血浆TNF的浓度。结果45例MODS患者的TNFB2等位基因频率为.7%,正常对照组为53%(P<0.05),TNFB2纯合子患者血浆TNF-α浓度和病死率高于杂合子及TNFB1合子患者(P<0.05);而两组的TNFα-308位点的基因频率及各基因型之间的血浆TNF-α浓度和病死率差异无统计学意义(P>0.05)。另外,两个TNF位点间存在连锁不平衡,单倍型分析提示,TNFB2:F1是MODS的危险因素,TNFB1:TNF1是MODS的保护性因素。结论TNFβ第一内含子+252位点的等基因TNFB2与MODS易感性相关。Objective To determine the relation between the susceptibility of MODS and the gene polymorphism of TNF.Methods The single base change of polymorphism in both TNF-α gene and TNF-β gene were analyzed between MODS patients and normal controls by PCR-RFLP.TNF_α and TNF_β plasma concentrations were detected by enzyme-linked immunosorbent assay.Results TNFB2 gene frequency increased significantly in MODS patients compared with normal contrds(67.7% VS 53%,P<0.05).Patients with TNFB2 homozygotes had higher TNF_α concentrations as well as mortality(P<0.05).No difference of allele frequencies or genotype distribution of TNF_α was found between MODS patients and normal contrds(P>0.05).In addition,a significant association was found between the two TNF gene polymorphisms.Haplotype analysis showed that the TNFB2:TNF1 haplotype was significantly risky factor of MODS and TNFB1:TNF1 haplotype was a protective factor of MODS.Conclusion TNFB2 is a susceptive marker for patients with increased TNF α concentration and poor prognosis in MODS.

关 键 词：肿瘤坏死因子 多脏器功能障碍综合征 基因多态性 聚合酶链式反应-限制性片段长度多态性 相关性研究 TNF-Α浓度 MODS ELISA方法 第一内含子 TNF-Β 308位点 等位基因频率 chain 血浆TNF 正常对照组 连锁不平衡 单倍型分析 

分 类 号：R363[医药卫生—病理学]