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目的探讨IFN治疗慢性乙型肝炎(CHB)患者的疗效与TNF-a启动子-238、-857、-863位点,IL-10启动子-1082、-592位点及黏病毒抵抗蛋白A(MxA)启动子-88位点单核苷酸多态性(SNP)的关系。方法305例CHB患者IFNa-1b治疗12个月,随访至停药后6个月判断疗效,分为持续应答(SR)和非持续应答(NSR)组。应用PCR及限制性片段长度多态性方法,检测TNF-a-238、-857、-863和IL-10-592、-1082及MxA-88位点的SNP。判断SNP与IFN疗效的关系。结果本研究失访43例。262例CHB患者IFNa-1b疗效SR为50例,占19.1%;NSR212例,占80.9%。在MxA-88位点,GT型分别与GG型、TT型患者IFN疗效比较,差异均有统计学意义(X~2=20.119,OR:5.302,95%CI:2.458～11.433,P<0.01;X~2=13.071,OR:4.110,95%CI:1.858～9.092,P<0.01)。在TNF-A-863位点,CC型分别与CA型、AA型患者疗效比较,差异均有统计学意义(X~2=29.628,OR:7.578,95%CI:3.444～16.672,P<0.01;X~2=13.543,OR:4.513,95%CI:1.966～10.357,P<0.01)。在TNF-a-857位点,CC与CT型患者疗效比较,差异有统计学意义(X~2=12.927,OR:0.293,95%CI:0.146～0.586,P<0.01)。在IL-10-592位点,AA与CC型患者疗效比较,差异有统计学意义(X~2=8.984,OR:3.380,95%CI:1.484～7.697,P<0.01)。结论MxA-88位点为GT杂合型,TNF-a-863 CC纯合型,IL-10-592 AA纯合型的CHB患者对IFNa-1b治疗反应好,可作为预测IFN疗效的参考指标之一。
OBJECTIVE: To investigate the effect of IFN treatment on patients with chronic hepatitis B (CHB) and the effect of TNF-a promoter at -238, -857 and -863 sites, IL-10 promoter -1082 and -592 sites and myxovirus resistance A MxA) promoter-88 site single nucleotide polymorphism (SNP). Methods One hundred and thirty-five patients with CHB were treated with IFNα-1b for 12 months. The follow-up was 6 months after discontinuation of treatment. The patients were divided into continuous response (SR) and non-sustained response (NSR) groups. The SNPs of TNF-a-238, -857, -863, IL-10-592, -1082 and MxA-88 were detected by PCR and restriction fragment length polymorphism. To determine the relationship between SNP and IFN efficacy. Results The study was lost to 43 cases. 262 cases of CHB patients with IFNa-1b response to SR was 50 cases, accounting for 19.1%; NSR212 cases, accounting for 80.9%. There were significant differences in the curative effect of IFN between GT type and GG type and TT type at MxA-88 locus (X ~ 2 = 20.119, OR: 5.302, 95% CI: 2.458 ~ 11.433, P <0.01; X ~ 2 = 13.071, OR: 4.110, 95% CI: 1.858 ~ 9.092, P <0.01). There were significant differences in the efficacy of CC genotype with CA genotype and AA genotype at TNF-A-863 locus (X ~ 2 = 29.628, OR: 7.578, 95% CI: 3.444 ~ 16.672, P <0.01) ; X ~ 2 = 13.543, OR: 4.513, 95% CI: 1.966 ~ 10.357, P <0.01). There was significant difference between the two groups in the level of TNF-a-857 in CT and CT (X ~ 2 = 12.927, OR: 0.293, 95% CI: 0.146-0.586, P <0.01). In IL-10-592, the difference was statistically significant between AA and CC patients (X ~ 2 = 8.984, OR: 3.380, 95% CI: 1.484-7.697, P <0.01). Conclusion The MxA-88 locus is GT heterozygous, TNF-a-863 CC homozygous, IL-10-592 AA homozygous CHB patients respond well to IFNa-1b therapy and can be used as a reference index to predict the efficacy of IFN one.