Variation of interleukin-28B at rs12979860 in injection drug users with HCV infection in a Chinese population

Abstract

Background: Hepatitis C virus (HCV) infection is a leading cause of liver disease globally. Recently, several genome-wide association studies have reported the strong association between single nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B) gene and the treatment outcome for chronic HCV infection. In Hong Kong, needle-sharing in injection drug users (IDU) continues to be a major route of HCV transmission. We conducted a follow-up study on HCV RNA-positive IDU to determine the genotype frequency of a SNP upstream of IL28B and their association with HCV genotype. Methods: A total of 273 IDU positive for anti-HCV and HCV RNA were included. Genomic DNA was extracted from whole blood samples, and the most strongly associated SNP near the IL28 gene, rs12979860, was determined by real-time PCR using a custom TaqMan genotyping kit. Results: The rs12979860 genotype distribution was CC in 237 IDU (86.8%), CT in 35 IDU (12.8%), and one case (0.4%) with TT genotype. The distribution of rs12979860 genotypes in the IDU population was in Hardy-Weinberg equilibrium (P = 0.810). Variation in the IL28B genotypes was not observed as compared with 300 healthy blood donors (CC: 87.0%, CT: 11.7%, and TT: 1.3%; P = 0.430). With regard to HCV genotype, HCV 1b and HCV 6a were the two commonest genotypes circulating in our local IDU population. Of the 105 IDU infected with HCV genotype 1 and 145 IDU with genotype 6, the frequency of the rs12979860 CC genotype was 81.9% and 88.3%, respectively, which were not different significantly (P = 0.509). Conclusion: In conclusion, the favorable rs12979860 CC genotype frequently observed in our Chinese population supports a potential role of incorporating IL28B SNP genotyping for the clinical workup of patients infected with HCV genotypes 1 and 6. Integrating the assessment of host and viral factors (age, gender, and HCV genotype) in combination with pre-treatment screening of IL28B rs12979860 polymorphism may provide useful prognostic information prior to interferon-based combination therapy for chronic HCV infection. This combined assessment may facilitate the development of new therapeutic approaches for the non-responders to conventional HCV therapies.