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

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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