Shen Chuanlai, Hu Ting, Shen Ling, Gao Lei, Xie Wei, Zhang Jianqiong
Genetics Research Center, South-East University Medical School, Nanjing, Jiangsu, China.
J Gastroenterol Hepatol. 2007 Nov;22(11):1898-903. doi: 10.1111/j.1440-1746.2006.04566.x.
The interferon sensitivity determining region (ISDR) in the non-structural 5A protein (NS5A) gene of hepatitis C virus genotype 1b (HCV-1b) has been demonstrated in Japanese patients; however, contradictory data have been reported from other parts of the world, particularly from Europe and the USA. This study investigated whether mutations in the ISDR of NS5A gene influence interferon efficacy in Chinese patients with chronic HCV-1b infection.
Forty-five Chinese patients with chronic HCV infection were enrolled in a retrospective study. Of these patients, 20 with HCV-1b infection completed an interferon monotherapy course and 6-month follow-up. The pretreatment mutations in the nucleic acid sequence of NS5A 2209-2248 (ISDR) of HCV-1b were identified by sequencing RT-PCR products followed by comparison with the prototype sequence (HCV-J). Correlation with the clinical efficacy of interferon alpha therapy was then analyzed retrospectively.
The statistical analysis indicated a significant correlation between the mutations in ISDR of HCV-1b and sustained virological response to interferon alpha treatment (P < 0.05), and an association of the mutations in ISDR with the pretreatment serum alanine aminotransferase levels (P < 0.01) in Chinese patients with chronic HCV-1b infection.
The results support the concept that the response of HCV-1b infected patients towards interferon therapy is influenced by the mutations within the ISDR of NS5A gene.
在日本患者中已证实丙型肝炎病毒1b型(HCV-1b)非结构5A蛋白(NS5A)基因中的干扰素敏感性决定区(ISDR);然而,世界其他地区,尤其是欧洲和美国,报道的数据却相互矛盾。本研究调查了NS5A基因ISDR中的突变是否会影响中国慢性HCV-1b感染患者的干扰素疗效。
45例中国慢性丙型肝炎感染患者纳入一项回顾性研究。其中,20例HCV-1b感染患者完成了干扰素单药治疗疗程及6个月的随访。通过对RT-PCR产物进行测序,然后与原型序列(HCV-J)比较,确定HCV-1b的NS5A 2209-2248(ISDR)核酸序列中的治疗前突变。随后回顾性分析与干扰素α治疗临床疗效的相关性。
统计分析表明,中国慢性HCV-1b感染患者中,HCV-1b的ISDR突变与干扰素α治疗的持续病毒学应答之间存在显著相关性(P<0.05),且ISDR突变与治疗前血清丙氨酸氨基转移酶水平相关(P<0.01)。
结果支持以下观点,即NS5A基因ISDR内的突变会影响HCV-1b感染患者对干扰素治疗的反应。