乌兹别克斯坦丙型肝炎病毒感染中IL28B基因多态性及其临床意义
IL28B polymorphisms and clinical implications for hepatitis C virus infection in Uzbekistan.
作者信息
Khudayberganova Dinara, Sugiyama Masaya, Masaki Naohiko, Nishida Nao, Mukaide Motokazu, Sekler Dildora, Latipov Renat, Nataliya Kan, Dildora Suyarkulova, Sharapov Said, Usmanova Guzal, Raxmanov Mahmarajab, Musabaev Erkin, Mizokami Masashi
机构信息
Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan; Institute of Virology, Ministry of Public Health of Uzbekistan, Tashkent, Uzbekistan.
Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
出版信息
PLoS One. 2014 Mar 24;9(3):e93011. doi: 10.1371/journal.pone.0093011. eCollection 2014.
AIMS
Genome-wide association studies highlighted single nucleotide polymorphisms (SNPs) within the IFNL3/IL28B locus predict the treatment outcome for patients with HCV. Furthermore, SNPs in newly discovered IFNL4 are shown to have population-specific correlation with spontaneous clearance of HCV. The aim of this study was to examine the prevalence and clinical significance of the outlined SNPs in a population from Central Asia, a multi-ethnic region with a developing economy and a high prevalence of HCV infection.
METHODS
One hundred and thirty-five chronic HCV patients from Uzbekistan were enrolled. DNA specimens were extracted from peripheral blood mononuclear cells and the IFNL3 SNPs (rs8099917, rs12979860) were genotyped by the Invader Plus assay, the TaqMan assay, and by direct sequence analysis. The IFL4 region (ss469415590) was sequenced.
RESULTS
Of the 135 patients that completed 24 or 48 weeks of treatment with Peg-IFN-α plus RBV, 87.4% were of Central Asian (CA) ancestry and 12.6% were of Eastern European (EE) ancestry. A non-virological response was observed in 21.2% of CA and in 35.3% of EE, respectively (p<0.32). The rs12979860 was strongly associated with treatment response (OR, 5.2; 95% CI, 1.9-14.6; p<0.004) in the overall sample; however, SNP rs8099917 was the most predictive of outcome for CA group (OR, 6.9; 95% CI, 2.6-18.0; p<0.002). The allele frequency of IFNL4 SNP, ss469415590, was identical with that of rs12979860 in all samples.
CONCLUSIONS
SNPs in IFNL3 and IFNL4 can be used to predict HCV treatment outcome in a population of Central Asian ancestry.
目的
全基因组关联研究表明，IFNL3/IL28B基因座内的单核苷酸多态性（SNP）可预测丙型肝炎病毒（HCV）患者的治疗结果。此外，新发现的IFNL4基因中的SNP显示出与HCV自发清除存在人群特异性关联。本研究的目的是在中亚人群中检测上述SNP的流行情况及其临床意义，中亚是一个多民族地区，经济发展中且HCV感染率高。
方法
招募了135名来自乌兹别克斯坦的慢性HCV患者。从外周血单个核细胞中提取DNA样本，并通过Invader Plus检测法、TaqMan检测法和直接序列分析对IFNL3 SNP（rs8099917、rs12979860）进行基因分型。对IFL4区域（ss469415590）进行测序。
结果
在完成聚乙二醇干扰素-α联合利巴韦林治疗24或48周的135名患者中，87.4%为中亚（CA）血统，12.6%为东欧（EE）血统。CA组和EE组分别有21.2%和35.3%观察到非病毒学应答（p<0.32）。在总体样本中，rs12979860与治疗反应密切相关（比值比，5.2；95%置信区间，1.9 - 14.6；p<0.004）；然而，SNP rs8099917对CA组的结局预测性最强（比值比，6.9；95%置信区间，2.6 - 18.0；p<0.002）。在所有样本中，IFNL4 SNP（ss469415590）的等位基因频率与rs12979860相同。
结论
IFNL3和IFNL4中的SNP可用于预测中亚血统人群的HCV治疗结果。
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