CAJ | 학술논문

目的探讨IRAK4(interleukin-1 receptor-associated kinase 4,IRAK4)基因单核苷酸多态性(single nucleotide polymorphisms,SNPs)与中国汉族人群严重脓毒症易感性和预后的相关性.方法收集2006年2月至2009年12月复旦大学附属中山医院急诊科收治的192例严重脓毒症患者进行研究.排除既往患有自身免疫性疾病、正在应用免疫抑制剂、AIDS和肿瘤患者.另外选择年龄和性别匹配的192名健康个体作为对照.本研究获得复旦大学附属中山医院伦理委员会同意.严重脓毒症患者根据30 d是否存活分为存活组和死亡组,存活组124例,死亡组68例.利用Hapmap中国人群数据库选择标签SNPs(tagSNPs),利用Primer 3软件设计引物；采用DNA抽提试剂盒提取外周血DNA,PCR-直接测序法进行SNPs分型.基因型频率和等位基因频率在各组之间的比较采用x2检验.结果 IRAK4基因7个tagSNPs等位基因频率分布在研究样本中均符合Hardy-Weinberg平衡.研究发现位于IRAK4基因外显子的SNP rs4251545(G/A)等位基因和基因型频率在严重脓毒症组和健康对照组之间差异具有统计学意义(等位基因P=0.015,基因型P=0.035),携带等位基因A的个体比携带等位基因G的个体更易患严重脓毒症(OR=1.69,95％ CI:1.10～2.58);7个tagSNPs的等位基因和基因型频率在死亡组和存活组中差异无统计学意义.结论IRAK4基因变异与中国汉族人群严重脓毒症易感性有关.
목적 탐토IRAK4(interleukin-1 receptor-associated kinase 4,IRAK4)기인단핵감산다태성(single nucleotide polymorphisms,SNPs)여중국한족인군엄중농독증역감성화예후적상관성.방법 수집2006년2월지2009년12월복단대학부속중산의원급진과수치적192례엄중농독증환자진행연구.배제기왕환유자신면역성질병、정재응용면역억제제、AIDS화종류환자.령외선택년령화성별필배적192명건강개체작위대조.본연구획득복단대학부속중산의원윤리위원회동의.엄중농독증환자근거30 d시부존활분위존활조화사망조,존활조124례,사망조68례.이용Hapmap중국인군수거고선택표첨SNPs(tagSNPs),이용Primer 3연건설계인물；채용DNA추제시제합제취외주혈DNA,PCR-직접측서법진행SNPs분형.기인형빈솔화등위기인빈솔재각조지간적비교채용x2검험.결과 IRAK4기인7개tagSNPs등위기인빈솔분포재연구양본중균부합Hardy-Weinberg평형.연구발현위우IRAK4기인외현자적SNP rs4251545(G/A)등위기인화기인형빈솔재엄중농독증조화건강대조조지간차이구유통계학의의(등위기인P=0.015,기인형P=0.035),휴대등위기인A적개체비휴대등위기인G적개체경역환엄중농독증(OR=1.69,95％ CI:1.10～2.58);7개tagSNPs적등위기인화기인형빈솔재사망조화존활조중차이무통계학의의.결론IRAK4기인변이여중국한족인군엄중농독증역감성유관.
Objective To investigate the possible association of IRAK4 polymorphisms with susceptibility to and prognosis of severe sepsis.Methods A total of 192 patients hospitalized in emergency department of Zhongshan Hospital from February 2006 to December 2009,and another 192 healthy volunteers were enrolled in this case-control study.Patients were excluded if they had metastatic tumors,autoimmune diseases,AIDS or received immunosuppressive drugs.This study was approved by the ethical committee of Zhongshan Hospital,Fudan University.Sepsis patients were divided into survival group(n =124)and non-survival group(n =68)according to the 30-day mortality.Primer 3 software was used to design the PCR and sequencing primers.Genomic DNA was extracted from peripheral blood mononuclear cells.Seven tagSNPs were selected based on the data of Chinese Han in Beijing from the Hapmap projectand genotyped by direct sequencing.We used x2 analysis to evaluate the significance of differences in genotype and allele frequencies between different groups.Results The distributions of all tagSNPs were consistent with Hardy-Weinberg equilibrium.The allele and genotype frequencies of rs4251545(G/A)were significantly different between severe sepsis and healthy control groups(P =0.015,P =0.035,respectively).Carriers of the rs4251545A had a higher risk for severe sepsis compared with carriers of the rs4251545G(OR =1.69,95％ CI:1.10-2.58).The allele and genotype frequencies of all SNPs were not significantly different between survivor group and non-survivor group.Conclusions These findings indicated that the variants in IRAK4 are significantly associated with severe sepsis susceptibility in the Chinese Han population.