GAO Ying, CHEN Rui, SONG Wen, CHEN Cheng-bin, QI Zhi-, JING Li, SUN Jin-ying and QIAN Shao. DNA M icroarray for M onitoring Genetic Variability ofHepatitis B virus during Lamivudine Therapy[J]. Virologica Sinica, 2003, 18(6): 523-529.
Citation: GAO Ying, CHEN Rui, SONG Wen, CHEN Cheng-bin, QI Zhi-, JING Li, SUN Jin-ying, QIAN Shao. DNA M icroarray for M onitoring Genetic Variability ofHepatitis B virus during Lamivudine Therapy .VIROLOGICA SINICA, 2003, 18(6) : 523-529.

利用基因芯片分析拉米夫定治疗过程中HBV DNA的基因变异

  • 摘要:依据乙型肝炎病毒(Hepatitis B virus;HBV)聚合酶基因序列研制HBV基因芯片,此芯片可分析HBV的 7个基因型、4种血清型和HBV聚合酶基因rtV173、rtL180、rtM204和rtV207位点的突变。利用此芯片对A、B 两组共计45例拉米夫定治疗12个月的患者进行服药前和服药后3、6、9、12个月的动态检测,其中C基因型 39例,且血清型均为adr;B基因型6例,其血清型均为adw。在完成全程检测的38例患者中,17例 升高 的A组出现1例拉米夫定耐药变异株,而21例 正常的B组出现4例变异株,且所有变异株均为rtM204 V/rtL180M,其中2例野生株和变异株共存。rtM204V变异最早在服药6个月时出现,随后出现rtL180M 变异。 lO份PCR产物测序分析表明,芯片检测结果与测序结果基本一致,仅在rtL173位点出现1例差异。进一步分析 HBV DNA变异与I-IBV DNA含量、ALT水平和HBeAg血清转换率的相关性,初步结果表明变异株的出现与治 疗过程中的DNA反弹呈正相关,而与起始HBV DNA水平、ALT值无关联。HBV基因芯片可初步用于HBV DNA 检测,可能是临床追踪评价抗病毒治疗效果的较好方法之一。 Abstract:The Hepatitis B virus(HBV)oligochip was made according to the sequence of HBVpolymerase gene.7 genotypes and 4 sero—subtypes of HBV,as well as position rtV173,~.L180,rtlVl21M,rtV207 in the reverse transcriptase(rt)domain of HBV polymerase,were detected with the chip.45patients were divided into A an d B groups according to their ALT levels.Serum samples for chipanalysis were obtained at 0,3,6,9,12 months of treatment.Among 45 patients,39 were genotype C andsubtype adr,6 were genotype B an d subtype adw.Among 38 patients whom were treated continuouslyfor 12 months,1 lamivudine resistant mutan t was discovered in 17 of A group with high ATL level,4varian ts were momtored in 21 of B group with normal ALT leve1.All varian ts were rtM 204V an drtL180M ,2 of them were mixed with HBV wild type .Th e rtM 204V mutan t was found at 6 months ofthempy,the~L180M mutant was detected afterward.Th e results obtained by sequencing ofthe 10 PCRproducts an d chip arraying were almost the same,the only diferent was that 1 varian t at position rtV173Was not detected by the gene chip.Further an alysing HBV DNA values,ALT levels an d HBeAgseroconversion in relation to HBV mutants,the results showed that a more rapid occurrence of varian tWas assoc iated with HBV DNA re—elevation.whereas not associated with HBV DNA values an d ALTlevels of pretreatm ent.Th e HBV gene chip could monitor genetic variability of HBV,it is a promi singmethod forevaluating effects oflamivudine therapy.

DNA M icroarray for M onitoring Genetic Variability ofHepatitis B virus during Lamivudine Therapy

  • Abstract:The Hepatitis B virus(HBV)oligochip was made according to the sequence of HBV polymerase gene.7 genotypes and 4 sero—subtypes of HBV,as well as position rtV173,~.L180,rtlVl21M, rtV207 in the reverse transcriptase(rt)domain of HBV polymerase,were detected with the chip.45 patients were divided into A an d B groups according to their ALT levels.Serum samples for chip analysis were obtained at 0,3,6,9,12 months of treatment.Among 45 patients,39 were genotype C and subtype adr,6 were genotype B an d subtype adw.Among 38 patients whom were treated continuously for 12 months,1 lamivudine resistant mutan t was discovered in 17 of A group with high ATL level,4 varian ts were momtored in 21 of B group with normal ALT leve1.All varian ts were rtM 204V an d rtL180M ,2 of them were mixed with HBV wild type .Th e rtM 204V mutan t was found at 6 months of thempy,the~L180M mutant was detected afterward.Th e results obtained by sequencing ofthe 10 PCR products an d chip arraying were almost the same,the only diferent was that 1 varian t at position rtV173 Was not detected by the gene chip.Further an alysing HBV DNA values,ALT levels an d HBeAg seroconversion in relation to HBV mutants,the results showed that a more rapid occurrence of varian t Was assoc iated with HBV DNA re—elevation.whereas not associated with HBV DNA values an d ALT levels of pretreatm ent.Th e HBV gene chip could monitor genetic variability of HBV,it is a promi sing method forevaluating effects oflamivudine therapy.

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    DNA M icroarray for M onitoring Genetic Variability ofHepatitis B virus during Lamivudine Therapy

    • 1. Collegeoflife sciences,NankaiUniversity,Tianjin 300071,China

    Abstract: Abstract:The Hepatitis B virus(HBV)oligochip was made according to the sequence of HBV polymerase gene.7 genotypes and 4 sero—subtypes of HBV,as well as position rtV173,~.L180,rtlVl21M, rtV207 in the reverse transcriptase(rt)domain of HBV polymerase,were detected with the chip.45 patients were divided into A an d B groups according to their ALT levels.Serum samples for chip analysis were obtained at 0,3,6,9,12 months of treatment.Among 45 patients,39 were genotype C and subtype adr,6 were genotype B an d subtype adw.Among 38 patients whom were treated continuously for 12 months,1 lamivudine resistant mutan t was discovered in 17 of A group with high ATL level,4 varian ts were momtored in 21 of B group with normal ALT leve1.All varian ts were rtM 204V an d rtL180M ,2 of them were mixed with HBV wild type .Th e rtM 204V mutan t was found at 6 months of thempy,the~L180M mutant was detected afterward.Th e results obtained by sequencing ofthe 10 PCR products an d chip arraying were almost the same,the only diferent was that 1 varian t at position rtV173 Was not detected by the gene chip.Further an alysing HBV DNA values,ALT levels an d HBeAg seroconversion in relation to HBV mutants,the results showed that a more rapid occurrence of varian t Was assoc iated with HBV DNA re—elevation.whereas not associated with HBV DNA values an d ALT levels of pretreatm ent.Th e HBV gene chip could monitor genetic variability of HBV,it is a promi sing method forevaluating effects oflamivudine therapy.

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