摘要
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.
出处
《中华传染病杂志》
CAS
CSCD
北大核心
2010年第5期286-289,共4页
Chinese Journal of Infectious Diseases
基金
基金项目:福建省卫生厅青年科研基金资助项目(2008-2-36)
关键词
肝炎
乙型
慢性
多态现象
遗传
启动区(遗传学)
干扰素A
受体
干扰素
基因型
Hepatitis B, chronic
Polymorphism, genetic
Promoter regions (genetics)
Interferon-alpha
Receptors, interferon
Genotype