Association between IPS- 1 polymorphisms and PEG- IFN treatment response in patients with HBeAg- positive chronic hepatitis B

Objective To investigate whether interferon- β promoter stimulator 1 (IPS- 1) gene polymorphisms could affect the treatment response to peginterferon alpha (PEG- IFN) in patients with HBeAg- positive chronic hepatitis B (CHB) .Methods A total of 212HBeAg- positive CHB patients treated with PEG- IFN monotherapy for 48 weeks were enrolled from the department of infectious diseases of Ruijin hospital in this study from January 2008 to December 2012.We collected peripheral blood from patients and extracted total genomic DNA.Genotype analysis was performed for 10 tag single nucleotide polymorphisms (SNPs) in IPS- 1 gene using the Sequenom MassArray system.Response was defined as cases showing hepatitis B virus (HBV) DNA level < 200 IU /ml, HBeAg seroconversion, and normal aminotransferase (ALT) levels after 48- week PEG- IFN therapy.The chi- square test was conducted to analyze the allele frequency and genotype distribution of IPS- 1 in both the response (R) and non- response (NR) groups.Binary logistic regression modeling was used to analyze the association of SNPs and haplotypes of IPS- 1 with treatment response.Results Of all the 212 patients, 95 (44.8%) were infected with HBV genotype B and 117 (55.2%) with HBV genotype C.There was a total response rate of 34.9% (74 /212) .Significant differences in genotype distributions of four SNPs (rs2326369, rs2464, rs6515831, and rs16989000) were observed between the R and NR groups (P < 0.05) .In multivariate analysis, three SNPs (rs2326369, rs6515831, and rs2464) were found to be independently associated with PEG- IFN efficacy after adjustment for sex, age, HBV genotype, family history, and baseline levels of HBV DNA and ALT: (1) rs2326369 CC genotype was independently associated with NR (OR = 0.51, 95% CI:0.28- 0.92, P = 0.026) ; (2) rs6515831 TT genotype was independently associated with R (OR = 2.08, 95% CI:1.12- 3.86, P = 0.020) ; (3) rs2464 CC genotype was independently associated with R (OR = 2.33, 95% CI:1.24- 4.37, P = 0.009) .Furthermore, two blocks were identified in this study, with block 1formed by rs16989000 and rs6515831 and block 2 formed by rs7272495, rs16989022, and rs2464.In multivariate analysis, haplotype AAC of block 2 was independently associated with R (OR = 2.05, 95% CI:1.09- 3.87, P = 0.026) .Conclusion Our study suggested that genetic variations in IPS- 1 are associated with the treatment response to PEG- IFN in HBeAg- positive CHB patients.For CHB patients treated with PEG- IFN, IPS- 1 genotyping may have a certain predictive value for curative effect.