title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Biochemistry, Faculty of Science, Ain Shams University.
authors.forename: Fahmy T
authors.initials: FT
authors.lastname: Ali
authors.affiliation: Department of Biochemistry, Faculty of Science, Ain Shams University.
authors.forename: Mohamed A M
authors.initials: MA
authors.lastname: Ali
authors.affiliation: Medical Research Laboratories, Armed Forces Medical Complex, Kobry Elqobba, Cairo, Egypt.
authors.forename: Mayada M A
authors.initials: MM
authors.lastname: Elgizawy
authors.affiliation: Internal Medicine Hospital, Armed Forces Medical Complex, Kobry Elqobba, Cairo, Egypt.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Elsawy
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004359:Drug Therapy, Combination; D004534:Egypt; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000235:genetics*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D016898:Interferon-alpha; D011994:Recombinant Proteins; C506895:SPP1 protein, human; D053495:Osteopontin; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a
keywords: Chronic hepatitis C; Interferons; Response; Secreted phosphoprotein 1; Single nucleotide polymorphisms