慢性乙型肝炎患者干扰素α受体1基因启动子多态性和干扰素应答的关系

目的 探讨慢性乙型肝炎患者的Ⅰ型干扰素受体1(IFNAR1)基因启动子多态性和IFN-α治疗应答之间的关系.方法 选择接受IFN-α治疗的慢性乙型肝炎患者61例,采用重组IFN-α2b 500万U,隔天肌内注射,疗程48周,观察应答情况,对入选患者的IFNAR1基因启动子区进行测序,计量资料采用t检验,计数资料采用卡方检验.结果 治疗的慢性乙型肝炎患者中,完全应答22例,部分应答8例,无应答31例.IFNAR1基因启动子区一408C/T、-3C/T、-77GT双核苷酸重复序列[-77(GT),]存在基因多态性,这三个位点基因多态性存在连锁,形成-408C/-77(GT)5/-3C等基因单体型.IFNAR1启动子区基因型为-408C/-77(GT)5/-3C及-408C/-77(GT)5/-3C的,基因型为-408C/-77(GT)5/-3C和非-408C/-77(GT)5/-3C的慢性乙型肝炎患者对IFN-α的应答率为61.0%,高于基因型为非-408C/-77(GT)5/-3C,非-408C/-77(GT)5/-3C患者的25.0%(X2=6.961,P=0.008).结论 IFNAR1启动子基因型为-408C/-77(GT)5/-3C及-408C/-77(GT)5/-3C的,-408C/-77(GT)5/-3C和非-408C/-77(GT)5/-3C的慢性乙型肝炎患者对IFN-α治疗应答较好,IFNAR1基因启动子多态性与慢性乙型肝炎患者的干扰素应答有关.

The association between promoter polymorphisms of interferon-alpha receptor-1 gene and the treatment response to interferon-alpha in patients with chronic hepatitis B

Objective To investigate the association between promoter polymorphisms of interferon-alpha receptor-1 (IFNAR1) gene and the treatment response to interferon-alpha (IFN-α) in patients with chronic hepatitis B (CHB). Methods Sixty-one CHB patients who consented to receive IFN-a therapy were enrolled in this study. The subjects were treated with recombinant IFN-α2b 500 MU intramuscular injection qod for 48 weeks. The treatment responses were monitored.Meanwhile, the promoters of IFNAR1 gene in these patients were sequenced. Measurement data were analyzed by t test and enumeration data were analyzed by Chi square test. Results Twenty-two treated patients achieved complete response. Eight patients achieved partial response and 31 had no response. Polymorphisms were identified in the promoter of IFNAR1 gene, which included C/T substitution at locus -408, C/T substitution at locus-3 and GT microsatellite repeat sequence at locus-77 [-77(GT)n]. The three polymorphisms were in linkage and composed some haplotypes,such as - 408C/-77(GT)5/-3C. The response rate to IFN-α in CHB patients with genotypes -408C/-77(GT)5/-3C, -408C/-77(GT)5/-3C, and-408C/-77(GT)5/-3C, non -408C/ - 77(GT)5/-3C in IFNAR1 gene promoter was higher than that in patients with genotype non -408C/-77(GT)5/-3C, non-408C/- 77(GT)5/- 3C (61. 0% vs 25. 0%, x2=6. 961, P =0.008). Conclusions CHB patients with genotype-408C/ - 77(GT)5/ - 3C, -408C/-77(GT)5/-3C and -408C/ -77(GT)5/ -3C, non -408C/ -77(GT)5/-3C in the promoter of the IFNAR1 gene are prone to have better response to IFN-a treatment. Polymorphisms in the promoter of IFN-αgene are associated with the treatment response to IFN-α in CHB patients.