乙型肝炎病毒相关性肾炎患儿乙型肝炎病毒S基因突变分析  

Mutation of hepatitis B virus S gene in children with hepatitis B virus-associated glomerulonephritis

作　　者：朱慧[1] 卢宏柱[1] 周建华[1] 吴衡生[1] 方峰[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院儿科,武汉430030

出　　处：《中华儿科杂志》2008年第5期378-381,共4页Chinese Journal of Pediatrics

基　　金：国家自然科学基金资助项目（30772360）;湖北省自然科学基金（2003AA301C91）

摘　　要：目的探讨乙型肝炎病毒（HBV）s基因的突变在乙型肝炎病毒相关性肾炎（HBV—GN）发病中的意义。方法从53例患儿（30例HBV—GN，5例。肾病伴HBV携带者，18例HBV携带者）的血清中提取DNA，以聚合酶链反应技术对HBV—DNA的S基因进行扩增，然后对扩增产物进行测序。结果（1）53例患儿血清型中52例为adw，在HBV携带组中1例为adr。（2）HBV基因型分型：30例HBV—GN中29例为B型，1例为E型；5例肾病HBV携带患儿为B型；18例HBV携带患儿中17例为B型，1例为c型。（3）30例HBV—GN中21例（70％）有点突变，共计17种突变，11种为错义突变，6种同义突变。16例（16／21，76．2％）点突变导致S抗原中氨基酸取代，其中11例（11／16，68．8％）涉及丝氨酸、苏氨酸、酪氨酸等潜在促分裂素原活化蛋白激酶（MAPK）和蛋白酪氨酸激酶（PTK）的磷酸化位点。5例。肾病伴HBV携带者中2例有同义突变，3例无任何突变；18例HBV携带者共有3例同义突变，无氨基酸改变。结论HBV—GN患儿大多存在HBVS基因变异并导致s抗原中氨基酸取代，其中主要涉及丝氨酸、苏氨酸、酪氨酸等MAPK和PTK的磷酸化位点，这些重要位点氨基酸的取代可能在HBV—GN的发病中起作用。Objective Hepatitis B virus-associated glomerulonephritis （HBV-GN） is an immune complex-mediated glomerulonephritis. The present study was conducted to identify HBV S gene mutation in children with HBV-GN. Methods Serum HBV DNA was extracted in 53 children, including 30 with HBV- GN, 5 with HBV-carring nephrosis （ control group 1 ）, and 18 HBV carriers （ control group 2 ）. HBV S gene sequence was amplified by polymerase chain reaction （PCR）. The PCR products were sequenced directly and compared with AY167097.1, an epidemic HBV strain in China. Results （ 1 ） The adw serotype of HBV was found in all the 30 cases with HBV-GN, 5 cases with HBV-carrying nephrosis and 17 HBV carriers except for 1, in whom adr serotype was identified. （ 2 ） HBV genotype B was found in 29 children with HBV- GN, 5 cases with HBV-carrying nephrosis and 17 HBV carriers, genotype E was found in a child with HBV- GN, and genotype C in an HBV carrier. （3） A total of 17 kinds of different single nucleotide change in HBV S gene were identified in 21 of 30 （ 70% ） HBV-GN patients. Among them, 16 of 21 （ 76. 2% ） nucleotide mutations resulted in amino acid substitution. It was interesting that most （11/16, 68.8% ） amino acid substitutions involved threonine, serine and tyrosine, the potential phosphorilation sites of mitogen-activated protein kinase （MAPK） and protein tyrosine kinase （PTK） in HBV protein. Single nucleotide changes which didn not result in amino acid substitution were found in 2 HBV-carrying nephrosis patients, 2 HBV carriers and 5 cases with HBV-GN. Conclusion Single nucleotide changes in HBV S gene were found in most children with HBV-GN. Most mutations in HBsAg resulted in amino acid substitutions involving threonine, serine and tyrosine, which may play a role in the pathogenesis of HBV-GN.

关 键 词：肾炎 肝炎 乙型 基因 突变 儿童 S基因 

分 类 号：R692.3[医药卫生—泌尿科学] R733.72[医药卫生—外科学]