传染病信息２００９年第２２卷第４期
图１ＨＢＶＲＴ基因相关位点代表性序列峰图
注：Ａ．Ｖ２１４野生Ｅ（ＧＴＡ）；Ｂ．Ｖ２１４Ａ（ＧＣＡ）；ｃ．Ｑ２１５野生（ＣＡＡ）；Ｄ．Ｑ２１５Ｓ（ＴＣＧ）；Ｅ．Ｑ２１５Ｈ（ＣＡＣ）；Ｆ．Ｑ２１５野生／Ｑ２１５Ｓ／Ｑ２１５Ｐ共ｆｊｑＣＡＧｆＩ＇ＣＧ／ＣＣＧ）
这也是目前睢一报道的ＴＤＦ临床耐药突变，但对此结果尚存在争议㈣。Ｋｏｚｉｅｌ等¨】对与ＴＤＦ等五种药物耐药相关的ＨＢＶ突变进行了总结（图２），其中Ｖ２１４Ａ和Ｑ２１５Ｓ突变株对ＴＤＦ敏感性下降为体外实验结果。最近又有研究表明：Ａ１８１Ｖ＋Ｎ２３６Ｔ联合突变株对ＴＤＦ的体外敏感性降低１０倍【ｔ３１，但这几种突变是否可引起临床耐药尚未得到证实。
我们对１７４０例ＣＨＢ患者血清ＨＢＶＲＴ基因进行了序歹Ⅱ测定，根据上述文献资料，重点对ＣＨＢ患者可能与ＴＤＦ耐药相关的Ａ１９４Ｔ以及可显著降低ＴＤＦ药敏的Ｖ２１４Ａ、Ｑ２１５ｓ和Ａ１８１Ｖ＋Ｎ２３４Ｔ进行了分析。共５４０例患者检出与核苷（酸）类似物耐药相关的突变，但未检测到Ａ１９４Ｔ突变。检出了３４例Ｖ２１４Ａ突变、２例Ｑ２１５Ｓ突变和１５例Ａ１８１Ｖ（或Ａ１８ｌＶ，Ｉ．）＋Ｎ２３６Ｔ突变，如前所述，与ＴＤＦ的耐药相关性还有待进一步明确。Ａ１８１Ｖ＋Ｎ２３６Ｔ是公认的氨基酸
功能域
（ｒｔｌＪｌａ３４４）
ＬｔＭＬＳＯＶｆｌＶ１７３ＬＭ２０４Ｖ／Ｉ／￥
Ｌ１８０Ｍ
１１６９Ｔ，Ａ１８１ＴＭ２０４Ｓ
Ｔ１８４ＳＱ２１５Ｓ，Ｖ２１４Ａ
ＡＤＶＡ１８ｌＴ，ＶＶ２１４ＡＮ２３６１ｍ２３８Ｄ
Ｖ８４Ｍ，￥８５ＡＱ２１５Ｓ
阴ｒＴ１８４ＧＳ２０２ＩＭ２５０Ｖ
１１６９Ｔ．Ｖ１７３Ｌ
Ｌ１８０Ｍ．Ｍ２０４Ｖ
ＴＤＦＡ１９４Ｔ
Ｖ２１４Ａ．Ｑ２１５Ｓ
ＬｄＴＭ２０４Ｉ
ｌＪｄＴ＋【ＡＭＬ１８０ＭＭ２０４Ｖ
图２与核苷（酸）类似物耐药相关的ＨＢＶＲＴ基因突变
1 740例慢性乙型肝炎患者替诺福韦酯耐药可能相关突变分析
作者：梁兆玲， 刘妍， 苏何玲， 孟玉华， 罗莉蓉， 王静， 戴久增， 姚增涛， 徐东平
作者单位：解放军传染病研究所,北京,100039
刊名：
传染病信息
英文刊名：INFECTIOUS DISEASE INFORMATION
年，卷(期)：2009,22(4)
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