Polymorphisms of CYP27B1 are associated with IFN efficacy in HBeAg-positive patients.

Abstract

Host single nucleotide polymorphisms were associated with antiviral therapy in CHB patients. The CYP27B1 gene, encoding 25(OH)D3 -1α hydroxylase, might activate 25(OH)D3 to 1,25(OH)2 D3 in kidney resulted in influencing the efficacy of interferon (IFN). The aim of the study was to investigate the association between CYP27B1 polymorphisms and the response to IFN in HBeAg-positive patients. Eighty-seven HBeAg-positive CHB patients infected with HBV genotype B or C were included in the study. All patients were treated with IFN at least 1year. According to the response to PEG-IFN therapy, they were divided into three groups: 16 complete responses (CR), 42 partial responses (PR), and 29 nonresponses (NR). Sanger-sequencing was utilized to genotype the CYP27B1 SNPs(rs4646536 and rs10877012). In logistic regression analysis, the frequency of rs4646536 CC genotype was observed to be higher in the NR group. Besides, the GG genotype of rs10877012 differed significantly among the three groups. The GG genotype was prevalent in patients with CR, and patients with TT genotype result in NR at the end of IFN treatment. The most common haplotype TG was independently associated with CR, after adjustment, and haplotype CT appeared to be associated with NR and PR, rather than CR. The data also showed that patients with baseline 1,25(OH)2 D3 > 39.39pg/mL had higher CR rates at the end of IFN therapy. These results suggested CYP28B1 gene polymorphisms may be independently associated with the efficacy of IFN in HBeAg-positive patients.