LMP2/LMP7基因多态性与人群中乙型肝炎病毒感染相关性研究  

Association between LMP2/LMP7 gene polymorphism and the infection of hepatitis B virus

作　　者：戴悦[1] 宁涛[2] 李坤[3] 綦素霞[3] 蒋明伟 柴庆波[1] 盖郁慧[1] 汪欣[1] 

机构地区：[1]北京大学第一医院输血科,北京10034 [2]北京大学临床肿瘤学院遗传室 [3]山东千佛山医院 [4]徐州第一人民医院

出　　处：《北京大学学报（医学版）》2005年第5期508-512,共5页Journal of Peking University:Health Sciences

基　　金：教育部教育振兴行动计划特殊专项(九八五工程和北京市科委肿瘤重大项目(H020920030130)资助~~

摘　　要：目的:探讨低相对分子质量蛋白酶体(lowmolecularweightproteasome,LMP)基因单核苷酸多态性(singlenucleotidepolymorphisms,SNP)与人群中乙型肝炎病毒(hepatitisBvirus,HBV)感染易感性的关联。方法:提取176例HBV感染者及208例健康人外周血基因组DNA,用PCR方法扩增LMP2/LMP7基因包含Codon60/Codon145两个多态性位点的片段,DNA直接测序法检测健康个体基因型,限制性片段长度多态性方法(restrictionfragmentlengthpolymorphism,RFLP)明确HBV感染者基因型。并采用PHASE1.0软件构建这两个多态性位点的个体单倍体型。以非条件Logistic回归校正混杂因素,并进行多态性与HBV感染风险关联的统计学分析。结果:LMP7基因多态性位点在两组人群中的差异有统计学意义(P<0.05),较之野生型Q/Q,杂合型Q/KOR=2.11(95%CI:1.36～3.26),纯合型K/KOR=2.66(95%CI:1.17～6.02);LMP2基因多态性位点在两组人群中差异无统计学意义(P>0.05)。在这两个位点所构建的单倍体型中,具有单倍体RK的个体在两组人群中差异有统计学意义(P<0.01,OR=1.81)。结论:LMP7基因的多态性与HBV感染有着显著的易感关联,虽然LMP2/LMP7基因多态性位点共同存在于单倍型时呈现一定拮抗作用,但结果提示,对于HBV感染的发生,LMP的多态性仍然是一个重要的易感危险因素。Objective： To elucidate whether thes antigen-processing gene （LMP2/LMP7） polymorphisms could influence the infection of hepatitis B virus. Methods： Genomic DNA of 176 patients infected with HBV and 208 healthy volunteers were extracted from the peripheral blood leukocytes. Polymorphisms of LMP genes in HBV patients were determined by polymerase chain reaction-restriction fragment length polymorphism （RFLP） , the controls by DNA sequencing. We used the software PHASE1.0 to construct the haplotypes of every individual. At last the unconditional Logistic regression model was used to analyze the statistical association of genotypes or haplotypes in two groups adjusted by gender and age. Results： The distributions of LMP2 genes, between cases and controls did not differ. However, LMP7 gene frequency in patients was higher than that in controls [ odds ratio 2.11 （95% confidence interval 1.36 - 3.26） ; 2.66 （95% confidence interval 1.17 - 6.02 ） , heterogenous or homologous respectively]. Similarly, we found the haplotype combinated by R-K had a significant difference in two groups [ odds ratio 1.81 （95% confidence interval 1.19- 2.76）]. Conclusion： These findings suggest that polymorphisms of LMP2/LMP7 gene is one of the important host factors which independently affect on the infection of hepatitis B virus.

关 键 词：肝炎病毒 乙型 多态性 单核苷酸 内肽酶类 

分 类 号：R512.62[医药卫生—内科学]