摘要
目的探讨IFN诱导的粘病毒抵抗蛋白A（MxA）和真核细胞起始因子2α调节区2（eIF-2α-reg2）基因的单核苷酸多态性（SNP）与CHB患者IFN治疗效果的关系。方法采用前瞻性研究方法，262例CHB患者签署知情同意书后予IFNα治疗12个月，随访至停药后6个月时评价疗效，分为持续应答和非持续应答。应用PCR及限制片段长度多态性的分析方法，检测患者MxA启动子-88、-123位点及eIF-2α-reg2的SNP，并比较SNP与IFN疗效的关系。结果262例CHB患者IFN治疗的应答情况为持续应答50例（19．1％），非持续应答212例（80．9％）。MxA启动子-88位点（G／T），GG型患者与GT型CHB患者IFN疗效比较，差异有统计学意义（OR5．3，95％置信区间2．46～11．43，P〈0．01）；TT型与GT型患者的疗效比较，差异有统计学意义（OR4．1，95％置信区间1.86～9．09，p〈0．01）。MxA启动子123位点（C／A）、eIF-2α-reg2位点（A／G）各基因型及MxA启动子-88与-123组成4种可能的单体型患者IFN疗效比较，差异均无统计学意义（P〉0．05）。结论MxA启动子-88位点为GT基因型的CHB患者对IFN治疗反应好，可作为IFN疗效的预测指标。
Objectives To identify the host single nucleotide polymorphisms （SNP） of myxovirus resistance A （MxA） protein and eukaryocyte initiation factor 2alfa regulatory region 2（eIF-2α -reg2） and to predict interferon （IFN） treatment responses in patients with chronic hepatitis B. Methods Two hundred sixty-two patients with chronic hepatitis B （CHB） were treated with interferon alfa （IFNα） for 12 months. Six months later the therapeutic effectiveness was evaluated. All the patients had signed a formal consent form. The patients were grouped into a sustained response （SR） group and a non-sustained response （NSR） group aec, ording to their responses to the IFN α treatment. Single nucleotide polymorphisms of the antiviral protein MxA promoter -88,- 123 and protein kinase（PKR） activated elF-2 α -reg2 sites were examined by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） and were compared with the responsiveness to IFN treatment of these CHB patients. Results Among the 262 patients, 212 （80.9%） were nonsustained responders to IFN α and 50 （19.1%） were sustained responders. The rate of sustained responders with GT heterozygote at MxA promoter -88 was higher than that of the GG genotype （OR： 5.3, 95% CI： 2.46- 11.43, P 〈 0.01） and also higher than that of the TT genotype （OR： 4.1, 95% CI： 1.86-9.09, P 〈 0.01）. There were no statistically significant differences in IFN therapeutic effectiveness among the patients with different genotypes at MxA promoter -123, eIF-2α-reg2 and haplotypes made by MxA promoter -88 Girl, and -123 C/ A allales （P 〉 0.05）. Conclusion Patients with GT genotype at MxA promoter -88 responded well to IFN treatment. SNP as a potential marker could be used to predict IFN treatment responses of patients with chronic hepatitis B.
出处
《中华肝脏病杂志》
CAS
CSCD
北大核心
2007年第3期187-191,共5页
Chinese Journal of Hepatology
基金
北京市自然科学基金（5062019）
