Natural killer cell responses play a crucial role in virus clearance by the innate immune system. Although the killer immunoglobulin-like receptor (KIR) in combination with its cognate human leukocyte antigen (HLA) ligand, especially
KIR2DL3-HLA-C1, is associated with both treatment-induced and spontaneous clearance of hepatitis C virus (HCV) infection in Caucasians, these innate immunity genes have not been fully clarified in Japanese patients. We therefore investigated 16 KIR genotypes along with
HLA-B and
-C ligands and a genetic variant of interleukin (IL) 28B (rs8099917) in 115 chronic hepatitis C genotype 1 patients who underwent pegylated-interferon-α2b (PEG-IFN) and ribavirin therapy.
HLA-Bw4 was significantly associated with a sustained virological response (SVR) to treatment (
P = 0.017; odds ratio [OR] = 2.50, ), as was the centromeric A/A haplotype of
KIR (
P = 0.015; OR 3.37). In contrast, SVR rates were significantly decreased in patients with
KIR2DL2 or
KIR2DS2 (
P = 0.015; OR = 0.30, and
P = 0.025; OR = 0.32, respectively). Multivariate logistic regression analysis subsequently identified the
IL28B TT genotype (
P = 0.00009; OR = 6.87, 95% confidence interval [CI] = 2.62 - 18.01),
KIR2DL2/HLA-C1 (
P = 0.014; OR = 0.24, 95% CI = 0.08 - 0.75),
KIR3DL1/HLA-Bw4 (
P = 0.008, OR = 3.32, 95% CI = 1.37 - 8.05), and white blood cell count at baseline (
P = 0.009; OR = 3.32, 95% CI = 1.35 - 8.16) as independent predictive factors of an SVR. We observed a significant association between the combination of
IL28B TT genotype and
KIR3DL1-
HLA-Bw4 in responders (
P = 0.0019), whereas
IL28B TT along with
KIR2DL2-HLA-C1 was related to a non-response (
P = 0.0067). In conclusion, combinations of
KIR3DL1/HLA-Bw4,
KIR2DL2/HLA-C1, and a genetic variant of the
IL28B gene are predictive of the response to PEG-IFN and ribavirin therapy in Japanese patients infected with genotype 1b HCV.
相似文献