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IL-10 和 IL-28B 的单核苷酸多态性作为预测 HCV 基因型 4 感染儿童 IFN 治疗反应的指标。

Single-nucleotide polymorphisms of IL-10 and IL-28B as predictors of the response of IFN therapy in HCV genotype 4-infected children.

机构信息

Department of Medical Biochemistry and Molecular Biology, Cairo University, Cairo 02, Egypt.

出版信息

J Pediatr Gastroenterol Nutr. 2013 Aug;57(2):155-60. doi: 10.1097/MPG.0b013e31828febf0.

Abstract

BACKGROUND AND AIMS

Single-nucleotide polymorphisms (SNPs) in the IL-10 gene (-1082 [rs1800896], -819 [rs3021097], and -592 [rs1800872]) and the IL-28B gene (rs12979860) in adults were shown to be associated with hepatitis C virus (HCV) clearance. The present study aimed to investigate the possible association of SNPs of IL-10 and IL-28B in predicting the treatment response of HCV genotype 4 in pediatric patients.

PATIENTS AND METHODS

A restriction fragment length polymorphism-polymerase chain reaction and real-time polymerase chain reaction techniques were used to genotype 34 pediatric patients with HCV genotype 4 for IL-10 and IL-28B SNPs, respectively. Patients received pegylated interferon-α/ribavirin for 48 weeks subdivided according to their response to treatment into responders and nonresponders; also, 20 healthy individuals served as controls.

RESULTS

A significant difference (P < 0.005) was observed in SNP of IL-28B rs12979860 frequencies between responders and nonresponders. In responders, CC genotype had greater frequency than CT and TT genotypes (60%, 30%, 10%), respectively, with C allele in its homozygous (CC) genotype more likely to respond to treatment than in its homozygous (TT) genotypes. SNPs of IL-10 at -819 (rs3021097) showed significant differences in their genotype frequencies between responders and nonresponders to therapy, and TT genotype had greater frequency in responders than CT and CC (55%, 20%, 25%), respectively. Genotypes with T allele (CT/TT) showed higher rates of response than those with no T allele (CC).

CONCLUSIONS

SNPs of the IL-28B gene at (rs12979860) CC genotype as well as the IL-10 gene SNPs at -819 (rs3021097)TT genotype can be used for predicting response to treatment before patients are prescribed the expensive pegylated interferon-α/ribavirin therapy.

摘要

背景与目的

成人白细胞介素-10 基因(-1082 [rs1800896]、-819 [rs3021097]和-592 [rs1800872])和白细胞介素-28B 基因(rs12979860)中的单核苷酸多态性(SNP)与丙型肝炎病毒(HCV)清除有关。本研究旨在探讨 IL-10 和 IL-28B 基因 SNP 在预测儿童丙型肝炎基因型 4 患者治疗反应中的可能作用。

患者和方法

采用聚合酶链反应技术和实时聚合酶链反应技术,对 34 例丙型肝炎基因型 4 的儿童患者进行白细胞介素-10 和白细胞介素-28B SNP 的基因分型。根据治疗反应将患者分为应答者和无应答者,接受聚乙二醇干扰素-α/利巴韦林治疗 48 周;另外,20 名健康个体作为对照。

结果

应答者和无应答者之间 IL-28B rs12979860 频率的 SNP 差异有统计学意义(P<0.005)。在应答者中,CC 基因型的频率高于 CT 和 TT 基因型(60%、30%、10%),C 等位基因在其纯合(CC)基因型中更有可能对治疗有反应,而在其纯合(TT)基因型中则不然。IL-10 基因-819 (rs3021097) SNP 的基因型频率在应答者和无应答者之间存在显著差异,TT 基因型在应答者中的频率高于 CT 和 CC(55%、20%、25%)。携带 T 等位基因(CT/TT)的基因型比不携带 T 等位基因(CC)的基因型有更高的应答率。

结论

IL-28B 基因(rs12979860)CC 基因型以及 IL-10 基因 SNP (rs3021097)TT 基因型可用于预测患者接受昂贵的聚乙二醇干扰素-α/利巴韦林治疗前的治疗反应。

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