Secreted Phosphoprotein 1 Promoter Genetic Variants Are Associated with the Response to Pegylated Interferon α Plus Ribavirin Combination Therapy in Egyptian Patients with Chronic Hepatitis C Virus Infection

Gut Liver. 2015 Jul;9(4):516-24. doi: 10.5009/gnl14162.

Abstract

Background/aims: The T-helper 1 (TH1) immune reaction is essential for the eradication of hepatitis C virus (HCV) during pegylated interferon α (PEG-IFN-α)- and ribavirin (RBV)-based therapy in chronic HCV patients. Secreted phosphoprotein 1 (SPP1) was shown to be a crucial cytokine for the initiation of a TH1 immune response. We aimed to investigate whether SPP1 single nucleotide polymorphisms (SNPs) may influence sustained virological response (SVR) rates.

Methods: Two SNPs in the promoter region of SPP1 at the -443 C>T and -1748 G>A loci were genotyped in 100 patients with chronic HCV genotype 4 infection using a TaqMan SNP genotyping assay.

Results: Sixty-seven patients achieved a SVR, and 33 patients showed no SVR. Patients carrying the T/T genotype at the -443 locus showed a significantly higher SVR rate than those carrying the C/T or C/C genotype (83.67% vs. 50.98%, p<0.001). At the -1748 locus, the SVR rate was significantly higher in patients with the G/G genotype than in those with the A/A genotype (88.89% vs. 52.63%, p=0.028) and in patients with the G/A genotype than in those with the A/A genotype (85.29% vs. 52.63%, p=0.001).

Conclusions: SPP1 SNPs at -443 C>T and -1748 G>A loci may be useful markers for predicting the response to PEG-IFN-α-2b plus RBV therapy in Egyptian patients with chronic HCV genotype 4 infection.

Keywords: Chronic hepatitis C; Interferons; Response; Secreted phosphoprotein 1; Single nucleotide polymorphisms.

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Biomarkers / blood
  • Drug Therapy, Combination
  • Egypt
  • Female
  • Genotype
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Osteopontin / genetics*
  • Polyethylene Glycols / therapeutic use*
  • Polymorphism, Single Nucleotide / genetics
  • Predictive Value of Tests
  • Promoter Regions, Genetic*
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use*
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Biomarkers
  • Interferon-alpha
  • Recombinant Proteins
  • SPP1 protein, human
  • Osteopontin
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2a