慢性乙型肝炎患者干扰素a受体1基因启动子多态性和干扰素应答的关系

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

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—a治疗应答之间的关系。方法选择接受IFN-a治疗的慢性乙型肝炎患者61例，采用重组IFN—a2b500万U，隔天肌内注射，疗程48周，观察应答情况，对人选患者的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-408C／T、-3C／T、-77GT双核苷酸重复序列[-77（GT）n]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—a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—a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。

Objective To investigate the association between promoter polymorphisms of interferon-alpha receptor-1 （IFNAR1） gene and the treatment response to interferon-alpha （IFN-a） 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-a2b 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 haptotypes, such as -408C/-77 （GT）5/-3C. The response rate to IFN-a 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 CHBpatients 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-a gene are associated with the treatment response to IFN a in CHB patients.