The association of LMP7 and TAP2 gene polymorphisms with treatment response to interferon/ribavirin in patients with genotype 1 chronic hepatitis C

Previous studies have highlighted the important role of genes related to antigen presentation in the spontaneous clearance of hepatitis C virus. The present study aimed to explore the association between TAP, LMP and tapasin gene polymorphism and treatment response in chronic hepatitis C virus (CHC) patients. Six single nucleotide polymorphisms in TAP, LMP and tapasin genes were genotyped among 352 Chinese genotype 1 CHC patients with pegylated interferon-alpha and ribavirin (pegIFN-alpha/RBV) treatment. There were 232 cases achieving sustained virological response (SVR), which yielded an SVR rate of 65.9%. LMP7 rs2071543 variant genotypes [additive model: odds ratio (OR), 0.52; 95% confidence interval (CI), 0.33-0.82; P=0.005] and TAP2 rs1800454 variant genotypes (additive model: OR, 0.66; 95% CI, 0.45-0.98; P=0.039) were suggested to decrease the possibility of achieving an SVR. After conducting combined effect analysis of rs2071543 and rs1800454, the authors found that the SVR rate was lower among patients carrying more unfavorable rs1800454-A and rs2071543-A alleles, and the SVR rate of carrying 3-4 alleles was 20%. In addition, carrying two unfavorable alleles led to significantly decreased possibility for SVR (OR, 0.30; 95% CI, 0.14-0.61; P=0.001). Multivariate stepwise analysis indicated that rs2071543, rs1800454, glucose, alpha-fetoprotein, platelets and baseline viral load were risk factors of SVR that were independent of each other. The area under the curve (AUC) consisting of all the above factors produced an AUC of 0.704 (95% CI, 0.647-0.761; P<0.001). The line charts indicated that the drop in viral load was significantly faster in GG patients than in GC/CC patients during the whole therapy, which was in accordance with the decline of viral load in rs2071543. The present study illustrated that the carriage of LMP7 rs2071543-AA and TAP2 rs1800454-AA had a negative effect on treatment response to pegIFN-alpha/RBV among genotype 1 patient with CHC in a Chinese Han population.