趋化因子CXCL10 G-201A单核苷酸多态性与HBV感染慢性化和重症化关系的研究  

Relationship between single nucleotide polymorphism of chemokine CXCL10 G-210A and the chronicity and severity of HBV infection

作　　者：刘立明[1,2] 许智慧[2] 刘妍[2] 钟彦伟[2] 毛远丽[2] 王海滨[2] 王慧芬[2] 徐东平[2] 

机构地区：[1]军事医学科学院,北京100850 [2]解放军302医院全军传染病研究所病毒性肝炎研究室

出　　处：《解放军医学杂志》2011年第1期39-41,共3页Medical Journal of Chinese People's Liberation Army

基　　金：国家“十一五”传染病重大专项子课题(2008ZX10002-005-6);国家重点基础研究发展计划课题(2007CB512803)

摘　　要：目的检测趋化因子CXCL10(IP-10)启动子区G-201A位点的单核苷酸多态性(SNP),探讨其与乙型肝炎病毒(HBV)感染慢性化及重症化的关系。方法采集302医院792例HBV感染患者血样,包括急性乙型肝炎(AHB)200例、轻中度慢性乙型肝炎(CHB-M)200例、重度慢性乙型肝炎(CHB-S)192例和慢加急肝衰竭(ACLF)200例,另采集300各正常人(NC)血样作为对照。提取DNA,PCR扩增与G-201位点变异连锁的C-1596区域片段,进行限制性片段长度多态性(PCR-RFLP)分析;同时从各组随机抽取400例样本,采用PCR产物直接测序法进行G-201位点区域片段的测序分析。对上述两种方法SNP分型结果的一致性进行分析。结果 G-201A的变异率为:AHB组17.77%,CHB-M组25.26%,CHB-S组26.59%,ACLF组21.28%,NC组13.82%,各组间总P=0.0037;相关性检验(P=0.0015)表明变异率与不同病程相关;经线性趋势检验,P=0.0029,Z=—2.9748,表明变异率随疾病进展呈现升高趋势。各组间两两比较发现,CHB-M、CHB-S、ACLF组与NC组之间的变异率有显著差异(P值分别为0.0024、0.0007、0.0428);CHB-S组与AHB组之间的变异率有显著差异(P=0.0488)。PCR产物直接测序法与PCR-RFLP法检测结果的一致率为98.68%,Kappa检验得出U=58.425,P<0.05,检测结果之间的一致性符合统计学要求。结论 IP-10启动子区G-201A变异与HBV感染慢性化相关,其与HBV感染重症化的关系尚需进一步研究。Objective To investigate the single nucleotide polymorphism（SNP） in the promoter of chemokine CXCL10 G-201A,and explore the relationship between the SNP and the chronicity and severity of hepatitis B virus（HBV） infection.Methods Blood samples were collected from 792 patients with HBV infection,including 200 with acute hepatitis B（AHB）,200 with mild/moderate chronic hepatitis B（CHB-M）,192 with severe chronic hepatitis B（CHB-S） and 200 with acute liver failure of chronic hepatitis（ACLF）,and 300 healthy people were enrolled as normal control（NC）.DNA were extracted and subjected to PCR amplification of fragment containing C-1596 site that links with G-201 variation,followed by restriction fragment length polymerase（RFLP） analysis.Simultaneously,400 samples were randomly extracted from various groups for direct sequencing of G-201 variation.The consistency of SNP typing results of the two methods was analyzed.Results Variation rates of G-201A were 17.77% for AHB group,25.26% for CHB-M group,26.59% for CHB-S group,21.28% for ACLF group,and 13.82% for NC group.The overall P value obtained from the general χ2 test among the 5 groups was 0.0037.The correlation test（P=0.0015） demonstrated that the variation rate was related to different disease status,and the linear trend test（P=0.0029,Z=-2.9748） indicated an increasing trend of variation rate with the disease progression.Paired comparison showed that the differences in variation rate between CHB-M and NC（P=0.0024）,CHB-S and NC（P=0.0007）,ACLF and NC（P=0.0428）,as well as CHB-S and CHB（P=0.0488） were statistically significant.Direct PCR sequencing showed 98.68% identity with the results from PCR-RFLP.Kappa test（U=58.425,P〈0.05） indicated that the consistency of the two assays met the statistical requirements.Conclusion The G-201A variation in CXCL10 promoter is related to chronicity of HBV infection,and the relations between the variation and the severity of HBV infection remains to be further clarified.

关 键 词：趋化因子 CXC 单核苷酸多态性 肝炎 乙型 慢性 

分 类 号：R512.62[医药卫生—内科学]