title: Integrative role of vitamin D related and Interleukin-28B genes polymorphism in predicting treatment outcomes of Chronic Hepatitis C.
abstract: BACKGROUND
  Improving prediction of treatment outcomes in chronic hepatitis C (CHC) genotype 4 (G4) is necessary to increase sustained viral response (SVR) rates. Vitamin D related and interferon stimulated genes are good candidates as they are recently crosstalk altering interferon response. Thus single nucleotide polymorphisms (SNPs) within some of these genes and multiple stepwise regression analysis including other independent predictors (IL28B(rs12979860), serum 25OH-vitamin D, serum alfa-fetoprotein (AFP)) were performed on a cohort of 200 Egyptian CHC patients treated with Pegylated interferon-alpha (Peg-IFN) plus ribavirin.
  
  
  METHODS
  SNPs in cytochrome P-450 (CYP2R1)(rs10741657AG), vitamin D receptor (VDR)(rs2228570AG, rs1544410CT), oligoadenylate synthetases-like (OASL)(rs1169279CT) and adenosine deaminases acting on RNA (ADAR)(rs1127309TC) genes were analyzed by real-time PCR.
  
  
  RESULTS
  The carrier state of A allele in VDR rs2228570 and CYP2R1 rs10741657 genes were independently associated with SVR [OR 6.453 & 3.536, p < 0.01 respectively]. Combining carriers of A allele in CYP2R1 and VDR genes with IL28B C/C genotype increased the probability of SVR from 80 % to reach 87.8 %, 93 % and 100 %. No relation was found between VDR rs1544410CT, ADAR rs1127309TC, OASL rs1169279CT polymorphisms and treatment outcome. Combining VDR rs2228570 A/A genotype with IL28B C/C genotype increased the probability of SVR from 82 % to reach 100 % and from 29 % to reach 80 % in C/T+ T/T IL28B genotype in none F4 liver disease patients.
  
  
  CONCLUSIONS
  Vitamin D related (VDR rs2228570 and CYP2R1 rs10741657) and IL28B rs12979860 genes polymorphisms accurately assure SVR in naïve CHC G4 patients treated with low cost standard therapy.
authors.affiliation: Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. marwa_omar25@hotmail.com.
authors.forename: M O
authors.initials: MO
authors.lastname: El-Derany
authors.affiliation: Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. nadia_hamdy@pharma.asu.edu.eg.com.
authors.forename: N M
authors.initials: NM
authors.lastname: Hamdy
authors.affiliation: Endemic Medicine Department & Hepatology Unit, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: N L
authors.initials: NL
authors.lastname: Al-Ansari
authors.affiliation: Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. hala.elmesallamy@hotmail.com.
authors.forename: H O
authors.initials: HO
authors.lastname: El-Mesallamy
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D000243:Adenosine Deaminase / Q000235:genetics; D000328:Adult; D000483:Alleles; D000998:Antiviral Agents / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018167:Receptors, Calcitriol / Q000235:genetics*; D012254:Ribavirin / Q000494:pharmacology; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D000095022:Interferon Lambda
chemical_list: D015088:2',5'-Oligoadenylate Synthetase; D000243:Adenosine Deaminase; D000998:Antiviral Agents; D003577:Cytochrome P-450 Enzyme System; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D016601:RNA-Binding Proteins; D018167:Receptors, Calcitriol; D012254:Ribavirin; D014807:Vitamin D; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C104450:25-hydroxyvitamin D; C115020:OASL protein, human; C000595356:ADAR protein, human