Impact of IL28B and OAS gene family polymorphisms on interferon treatment response in Caucasian children chronically infected with hepatitis B virus.
Impact of IL28B and OAS gene family polymorphisms on interferon treatment response in Caucasian children chronically infected with hepatitis B virus.
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IL28B和OAS基因家族多态性对高加索儿童的干扰素治疗反应的影响长期感染了丙型肝炎病毒。
DOI：
10.3748/wjg.v22.i41.9186
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发表时间：
2016-11-07
影响因子：
4.3
通讯作者：
Tretyn A
中科院分区：
文献类型：
--
作者：
Domagalski K;Pawłowska M;Zaleśna A;Pilarczyk M;Rajewski P;Halota W;Tretyn A
探讨IL 28 B和OAS基因多态性对儿童慢性B型肝炎干扰素治疗反应的影响。我们招募了52名患有B e抗原阴性的慢性B型肝炎（CH B）的儿童（年龄在4至18岁之间），他们接受了聚乙二醇干扰素α治疗48周。研究了OAS 1（rs 1131476）、OAS 2（rs 1293747）、OAS 3（rs 2072136）、OASL（rs 10849829）和IL 28 B（rs 12979860、rs 12980275和rs 8099917）基因的单核苷酸多态性，以检查其与儿科患者对IFN治疗反应的相关性。我们采用了两个治疗反应标准，即达到B型肝炎病毒（HBV）DNA水平< 2000 IU/mL和ALT活性正常化（< 40 IU/L）。为了进行分析，我们比较了患者在治疗后24周随访时测量的部分缓解（PR）和完全缓解（CR）。PR和CR率分别为80.8%和42.3%。年龄、性别和肝脏组织学等因素对缓解类型（部分或完全）没有影响。基线HBV DNA和ALT水平升高与PR和CR率降低有显著相关性（P < 0.05）。等位基因关联分析显示，只有IL-28 B rs 12979860（C vs T）和IL-28 B rs 12980275（A vs G）标记物显著影响PR的实现（分别为P = 0.021，OR = 3.3，95%CI：1.2-9.2和P = 0.014，OR = 3.7，95%CI：1.3-10.1）。然而，在基因型分析中，仅IL-28 B rs 12980275与PR显著相关（AA vs AG-GG，P = 0.014，OR = 10.9，95%CI：1.3-93.9）。CR相关分析显示IL 28 B rs 12979860的TT基因型仅存在于无CR组（P = 0.033），而OASL rs 10849829的AA基因型在无CR组中显著更常见（P = 0.044，OR = 0.26，95%CI：0.07-0.88）。单倍型分析显示PR和CR与OAS单倍型之间存在显著相关性（分别为P = 0.0002和P = 0.001），但未观察到与IL 28 B单倍型的相关性。IL 28 B和OAS多态性与干扰素治疗的CHB儿童的不同临床结局相关
To investigate the impact of IL28B and OAS gene polymorphisms on interferon treatment responses in children with chronic hepatitis B. We enrolled 52 children (between the ages of 4 and 18) with hepatitis B e antigen-negative chronic hepatitis B (CHB), who were treated with pegylated interferon alfa for 48 wk. Single nucleotide polymorphisms in the OAS1 (rs1131476), OAS2 (rs1293747), OAS3 (rs2072136), OASL (rs10849829) and IL28B (rs12979860, rs12980275 and rs8099917) genes were studied to examine their associations with responses to IFN treatment in paediatric patients. We adopted two criteria for the therapeutic response, achieving an hepatitis B virus (HBV) DNA level < 2000 IU/mL and normalization of ALT activity (< 40 IU/L). To perform the analyses, we compared the patients in terms of achieving a partial response (PR) and a complete response (CR) upon measurement at the 24-wk post-treatment follow-up. The PR and CR rates were 80.8% and 42.3%, respectively. Factors such as age, gender and liver histology had no impact on the type of response (partial or complete). A statistically significant relationship between higher baseline HBV DNA and ALT activity levels and lower rates of PR and CR was shown (P < 0.05). The allele association analysis revealed that only the IL-28B rs12979860 (C vs T) and IL28B rs12980275 (A vs G) markers significantly affected the achievement of PR (P = 0.021, OR = 3.3, 95%CI: 1.2-9.2 and P = 0.014, OR = 3.7, 95%CI: 1.3-10.1, respectively). However, in the genotype analysis, only IL-28B rs12980275 was significantly associated with PR (AA vs AG-GG, P = 0.014, OR = 10.9, 95%CI: 1.3-93.9). The association analysis for CR showed that the TT genotype of IL28B rs12979860 was present only in the no-CR group (P = 0.033) and the AA genotype of OASL rs10849829 was significantly more frequent in the no-CR group (P = 0.044, OR = 0.26, 95%CI: 0.07-0.88). The haplotype analysis revealed significant associations between PR and CR and OAS haplotype (P = 0.0002 and P = 0.001, respectively), but no association with IL28B haplotype was observed. IL28B and OAS polymorphisms are associated with different clinical outcomes in CHB children treated with interferon.
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影响因子：
120.7
作者：
Chen, CJ;Yang, HI;Iloeje, UH
通讯作者：
Iloeje, UH
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影响因子：
9.8
作者：
Bonnevie-Nielsen, V;Field, LL;Pociot, F
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Pociot, F
影响因子：
29.4
作者：
Iloeje, UH;Yang, HI;Chen, CJ
通讯作者：
Chen, CJ
影响因子：
29.4
作者：
Manesis, EK;Hadziyannis, SJ
通讯作者：
Hadziyannis, SJ
影响因子：
2.4
作者：
Chen J;Wang W;Li X;Xu J
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