生物谷报道：来自浙江大学医学院附属第一医院麻醉学系的研究人员通过300多例病患及对照的研究，发现了对于严重败血症易感性和致命后果都具有极大关系的一个基因组变异，这为DEFB1在严重败血症的发病机理中扮演的重要角色提出了进一步的证据。这一研究成果公布在Genes and Immunity（Nature出版社出版的期刊之一）。
文章的通讯作者是浙江大学附属第一医院的方向明教授。
败血症（sepsis）是指病原菌及其毒素侵入血流所引起的临床综合征。病程中常有炎症介质的激活和释放，引起高热、寒战、心动过速呼吸急促、皮疹和神志改变等一系列临床症状，严重者可引起休克、DIC和多器官功能衰竭。即使给予适当的抗生素治疗，病死率仍较高，许多名人都是死于这种疾病，比如我们熟悉的白求恩，
这种疾病从机理上来说是一种针对感染的系统炎症反应综合症（systemic inflammatory response syndrome），人β-防御素1（human β-defensin 1，DEFB1)是这些炎症和感染反应中的一个复合功能因子，这种抗微生物肽主要分布在脊椎动物的皮肤、粘膜等上皮组织，构成机体抵御微生物侵袭的第一道化学屏障，在组织烧伤等创伤感染中发挥重要作用。
在这篇文章中，为了了解DEFB1基因组突变是否与严重败血症的易感性及疾病程度有关系，研究人员进行了211个病患及157个健康对照的研究，结果发现一个对于严重败血症易感性和致命后果都具有极大关系的多态性：-44G/C（分别为P=0.0049, odd ratio (OR) 1.971 和P=0.002, OR 2.406）。另外单体型（Haplotype）-20A/-44C/-52G则表现出对抗严重败血症的作用，而-20G/-44G/-52G却是严重败血症致死的一个危险因子。这些研究发现为DEFB1在严重败血症的发病机理中扮演的重要角色提出了进一步的证据。
原始出处：
Genes and Immunity advance online publication 17 May 2007; doi: 10.1038/sj.gene.6364401
Genomic variations within DEFB1 are associated with the susceptibility to and the fatal outcome of severe sepsis in Chinese Han population
Q-X Chen1, C Lv1, L-X Huang1, B-L Cheng1, G-H Xie1, S-J Wu1 and X-M Fang1
1Department of Anesthesiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
Correspondence: Dr X-M Fang, Department of Anesthesiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou 310003, China. E-mail: xiangming_fang@163.com
Received 31 January 2007; Revised 9 April 2007; Accepted 16 April 2007; Published online 17 May 2007.
Abstract
Sepsis is a systemic inflammatory response syndrome to infection. Human -defensin 1 (DEFB1) is a multifunctional mediator in infection and inflammation, which has been largely explored in ex vivo studies. The present case–control study was designed to investigate whether DEFB1 genomic variations are associated with the susceptibility to and the outcome of severe sepsis in 211 patients with severe sepsis and 157 ethnic-matched healthy controls. After correcting for multiple testing, the -44G/C was the only polymorphism found to show significant associations with both the susceptibility to and the fatal outcome of severe sepsis (P=0.0049, odd ratio (OR) 1.971 and P=0.002, OR 2.406, respectively). Haplotype -20A/-44C/-52G showed a protective role against severe sepsis (P=0.0066, OR 0.6751), whereas haplotype -20G/-44G/-52G served as a risk factor for the fatal outcome of severe sepsis (P=0.0052, OR 2.427). These findings provide further evidence that -defensin 1 may play a role in the pathogenesis of severe sepsis.
Keywords:
human -defensin 1, DEFB1, SNP, haplotype, severe sepsis, association study
附：
姓名: 方向明
性别: 女
单位: 医学院
职称: 教授
研究方向 全身性感染/器官功能损伤发生发展机制及防治
邮件: xiangming_fang@163.com, xm_fang@hotmail.com
