IL28B, HLA-C and KIR variants additively predict response to therapy in chronic hepatitis C virus infection in a european cohort: A cross-sectional study

摘要: Background To date, drug response genes have not proved as useful in clinical practice was anticipated at the start of genomic era. An exception is treatment chronic hepatitis C virus (HCV) genotype 1 infection with pegylated interferon-alpha and ribavirin (PegIFN/R). Viral clearance achieved 40%–50% patients. Interleukin 28B (IL28B) predicts treatment-induced spontaneous clearance. To improve predictive value this genotype, we studied combined effect variants IL28B human leukocyte antigen (HLA-C), its ligands killer immunoglobulin-like receptors (KIR), which previously been implicated HCV viral control. Methods Findings We genotyped (CHC) patients PegIFN/R (n = 417) failure 493), 234 individuals clearance, for HLA-C C1 versus C2, presence inhibitory activating KIR genes, two SNPs, rs8099917 rs12979860. All were Europeans or European descent. SNP “G” associated absence (odds ratio [OR] 2.19, p 1.27×10−8, 1.67–2.88) (OR 3.83, 1.71×10−14, 2.67–5.48) HCV, rs12979860, slightly lower ORs. The C2C2 also over-represented who failed 1.52, 0.024, 1.05–2.20), but Prediction improved from 66% to 80% using both cohort 3.78, 8.83×10−6, 2.03–7.04). There evidence that KIR2DL3 KIR2DS2 carriage altered combination IL28B. Conclusions Genotyping IL28B, HLA-C, improves prediction response. These findings support a role natural (NK) cell activation partially mediated by IL28B.