摘要
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 relationship between interferon （IFN） therapeutic effects and the host single nucleotide polymorphisms（SNP） of tumor necrotic factor（TNF）-α-promoter-238, -857, -863, interleukin （IL）-10-promoter-1082, -592 and myxovirus resistance protein A （MxA） promoter-88 in patients with chronic hepatitis B（CHB）. Methods Three hundreds and five patients with CHB were treated with IFNα-lb for 1 year and followed up for 6 months to evaluate the therapeutic effects. All the patients were divided into two groups： sustained response（SR） group and non-sustained response（NSR） group. The SNP of TNF-α-238, -857, -863, IL-10 -592, -1082 andMxA promoter -88 were examined by polymerase chain reaction restriction fragment length polymorphisms（PCR-RFLP） to determine the relationship between SNP and IFN therapeutic effects. Results Forty three patients were lost follow up. Among 262 patients with CHB, 50（19. 1%） cases were SR and 212（80. 9%） were NSR to IFNα-1b treatment. Regarding MxA-88 site, there were significant differences of SR rate in CHB patients between GT heterozygote and GG or TT genotype, respectively （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 also significant differences of SR rate between TNF-a-863 genotype CC and CA or AA, respectively （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 differences of SR rate between TNF-α-857 genotype CC and CT （X^2 = 12. 927, OR： 0. 293, 95%CI： 0. 146-0. 586, P 〈 0. 01）. Regarding IL-10-592 site, there was significant differences of SR rate between AA and CC （X^2 = 8. 984, OR： 3. 380, 95% CI： 1. 484-7. 697, P 〈 0.01）. Conclusions Patients with GT heterozygous genotype at MxA-88, homozygous CC at TNF-α 863 and AA at IL-10-592 respond better to IFNα-1b treatment, which can be one of the pr
出处
《中华传染病杂志》
CAS
CSCD
北大核心
2007年第11期675-680,共6页
Chinese Journal of Infectious Diseases
基金
北京市科委病毒性肝炎重大项目(H020920020690)
