Evaluation of MICA variations and serum MICA as prognostic factors for Chronic hepatitis C patients

在这里，我们对1618例HCV诱导的肝硬化（LC）病例和4854例CHC患者进行了全基因组关联研究。我们发现主要组织相容性复合体（MHC）区域内的两个SNPs rs 910049和rs3135363与CHC向LC的进展显著相关（Pcombined=9. 05）。15 x10 ^<-11>和1。45x10^<-10>）。我们还在启动子区筛选了15个候选SNP，发现SNP rs 2596538位于2.云母基因上游8 kb改变了转录因子SP1与包括该SNP的基因组区域的结合。此外，通过荧光素酶报告基因分析，在体外观察到G等位基因的较高转录活性，与HCV诱导的具有G等位基因的HCC患者中较高的可溶性云母（sMICA）水平一致。总之，我们确定了MHC区域内的多种遗传变异作为CHC患者预后/预测生物标志物的关键作用。

Here we conducted a genome-wide association study using 1618 HCV-induced liver cirrhosis(LC) cases and 4, 854 CHC patients. We found that two SNPs within the major histocompatibility complex(MHC) region, rs910049 and rs3135363, and were significantly associated with the progression from CHC to LC(Pcombined=9. 15x10^<-11> and 1. 45x10^<-10>). We also screened 15 candidate SNPs at the promoter region and found that SNP rs2596538 located at 2. 8 kb upstream of the MICA gene altered the binding of transcription factor SP1 to the genomic region including this SNP. Moreover, higher transcriptional activity of G allele was observed in vitro by luciferase reporter assay, concordant with higher soluble MICA(sMICA) level among HCV-induced HCC patients with G allele. In summary, we identified the crucial roles of multiple genetic variations within the MHC region as prognostic/predictive biomarkers for CHC patients