生物谷報(bào)道：來自浙江大學(xué)醫(yī)學(xué)院附屬第一醫(yī)院麻醉學(xué)系的研究人員通過300多例病患及對(duì)照的研究,，發(fā)現(xiàn)了對(duì)于嚴(yán)重?cái)⊙Y易感性和致命后果都具有極大關(guān)系的一個(gè)基因組變異,，這為DEFB1在嚴(yán)重?cái)⊙Y的發(fā)病機(jī)理中扮演的重要角色提出了進(jìn)一步的證據(jù)。這一研究成果公布在Genes and Immunity（Nature出版社出版的期刊之一）,。
文章的通訊作者是浙江大學(xué)附屬第一醫(yī)院的方向明教授,。
敗血癥（sepsis）是指病原菌及其毒素侵入血流所引起的臨床綜合征。病程中常有炎癥介質(zhì)的激活和釋放,，引起高熱,、寒戰(zhàn)、心動(dòng)過速呼吸急促,、皮疹和神志改變等一系列臨床癥狀,，嚴(yán)重者可引起休克、DIC和多器官功能衰竭,。即使給予適當(dāng)?shù)目股刂委?，病死率仍較高,，許多名人都是死于這種疾病，比如我們熟悉的白求恩,，
這種疾病從機(jī)理上來說是一種針對(duì)感染的系統(tǒng)炎癥反應(yīng)綜合癥（systemic inflammatory response syndrome）,，人β-防御素1（human β-defensin 1，DEFB1)是這些炎癥和感染反應(yīng)中的一個(gè)復(fù)合功能因子,，這種抗微生物肽主要分布在脊椎動(dòng)物的皮膚,、粘膜等上皮組織，構(gòu)成機(jī)體抵御微生物侵襲的第一道化學(xué)屏障,，在組織燒傷等創(chuàng)傷感染中發(fā)揮重要作用,。
在這篇文章中，為了了解DEFB1基因組突變是否與嚴(yán)重?cái)⊙Y的易感性及疾病程度有關(guān)系,，研究人員進(jìn)行了211個(gè)病患及157個(gè)健康對(duì)照的研究，結(jié)果發(fā)現(xiàn)一個(gè)對(duì)于嚴(yán)重?cái)⊙Y易感性和致命后果都具有極大關(guān)系的多態(tài)性：-44G/C（分別為P=0.0049, odd ratio (OR) 1.971 和P=0.002, OR 2.406）,。另外單體型（Haplotype）-20A/-44C/-52G則表現(xiàn)出對(duì)抗嚴(yán)重?cái)⊙Y的作用,，而-20G/-44G/-52G卻是嚴(yán)重?cái)⊙Y致死的一個(gè)危險(xiǎn)因子。這些研究發(fā)現(xiàn)為DEFB1在嚴(yán)重?cái)⊙Y的發(fā)病機(jī)理中扮演的重要角色提出了進(jìn)一步的證據(jù),。
原始出處：
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: [email protected]
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
性別: 女
單位: 醫(yī)學(xué)院
職稱: 教授
研究方向 全身性感染/器官功能損傷發(fā)生發(fā)展機(jī)制及防治
郵件: [email protected], [email protected]
