白细胞介素-28B基因的Rs12979860和rs8099917单核苷酸多态性：丙型肝炎病毒感染的白种人患者中的同步基因分型
Rs12979860 and rs8099917 single nucleotide polymorphisms of interleukin-28B gene: simultaneous genotyping in caucasian patients infected with hepatitis C virus.
作者信息
Sticchi L, Di Biagio A, Rappazzo E, Setti M, De Rosa G, De Hoffer L, Nicolini L, Prinapori R, Bruzzone B
机构信息
Department of Health Sciences, University of Genoa, Italy.
Infectious Diseases, IRCCS AOU San Martino, Genoa, Italy.
出版信息
J Prev Med Hyg. 2013 Jun;54(2):83-6.
INTRODUCTION
Recent studies have demonstrated the role of the interleukin 28B (IL28B) polymorphisms in predicting treatment induced and spontaneous clearance from Hepatitis C virus (HCV) infection, suggesting the possibility of tailored therapy in HCV infected patients. Genome-wide association studies have shown that single nucleotide polymorphisms (SNPs) near IL 28B gene on chromosome 19 are strong predictors of sustained virologic response (SVR) to pegylated interferon and ribavirin. This study was aimed at analyzing the co-prevalence of two common and clinically significant SNPs in a cohort of Ligurian patients.
METHODS
Two SNPs (rs12979860, rs8099917) were genotyped in the IL28B locus from 175 DNA samples collected from HCV-infected consecutive patients in a Laboratory of Liguria Region, northern Italy. A real-time polymerase chain reaction in a Corbett Research Termocycler (Rotor Gene 3000A) by fluorescent probes (Fast Set IL 28B, Arrow Diagnostics) was used for the detection, according to the manufacturer's instructions.
RESULTS
Carriers of rs12979860CT genotype predominated (87/175, 50%), homozygotes for allele C were 68/175 (39%) and the remaining were homozygotes for IFN-resistant allele T (11%). As for the rs8099917 SNP, genotypes were thus distributed: 96/175 (55%) carried the rs8099917 TT genotype, whereas 70/175 (40%) and 9/175 (5%), were heterozygotes or homozygotes for the G allele. The variants rs12979860CC and rs8099917TT were found in 39% and 54% of overall patients with HCV genotype 1, respectively. The combined assessment of examined SNPs resulted in three most prevalent genotypes (rs12979860CC/rs8099917TT, rs12979860CT/rs8099917TG and rs12979860CT/rs8099917TT) with a frequency of 35%, 31% and 18%, respectively.
DISCUSSION
Recent findings demonstrated that in carriers of rs12979860CT the determination of additional genotype of rs8099917 SNP could significantly improve the prediction of SVR. In our study cohort carriers of rs12979860CT represented 50% of all patients, who could take advantage with respect to SVR prediction by further determination of the rs8099917 SNP. The simultaneous genotyping of two IL28B SNPs should thus be recommended in HCV infected patients prior to treatment initiation.
引言
近期研究已证实白细胞介素28B（IL28B）基因多态性在预测丙型肝炎病毒（HCV）感染的治疗诱导清除和自发清除中的作用，这提示了对HCV感染患者进行个体化治疗的可能性。全基因组关联研究表明，19号染色体上IL28B基因附近的单核苷酸多态性（SNP）是聚乙二醇干扰素和利巴韦林持续病毒学应答（SVR）的强预测指标。本研究旨在分析利古里亚患者队列中两种常见且具有临床意义的SNP的共发生率。
方法
在意大利北部利古里亚地区的一个实验室，对从连续的HCV感染患者收集的175份DNA样本的IL28B基因座中的两个SNP（rs12979860、rs8099917）进行基因分型。根据制造商的说明，使用Corbett Research Termocycler（Rotor Gene 3000A）中的实时聚合酶链反应和荧光探针（Fast Set IL 28B，Arrow Diagnostics）进行检测。
结果
rs12979860 CT基因型携带者占主导（87/175，50%），等位基因C的纯合子为68/175（39%），其余为对干扰素耐药的等位基因T的纯合子（11%）。至于rs8099917 SNP，基因型分布如下：96/175（55%）携带rs8099917 TT基因型，而70/175（40%）和9/175（5%）为G等位基因的杂合子或纯合子。rs12979860 CC和rs8099917 TT变异分别在39%和54%的HCV 1型总体患者中发现。对检测的SNP进行联合评估产生了三种最常见的基因型（rs12979860 CC/rs8099917 TT、rs12979860 CT/rs8099917 TG和rs12979860 CT/rs8099917 TT），频率分别为35%、31%和18%。
讨论
近期研究结果表明，在rs12979860 CT携带者中，rs8099917 SNP额外基因型的确立可显著改善SVR的预测。在我们的研究队列中，rs12979860 CT携带者占所有患者的50%，通过进一步确定rs8099917 SNP，他们在SVR预测方面可能会受益。因此，对于HCV感染患者，在开始治疗前应建议同时对两个IL28B SNP进行基因分型。
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