title: Association of SNPs in interferon receptor genes in chronic hepatitis C with response to combined therapy of interferon and ribavirin.
abstract: Hepatitis C Virus is one of the main reasons for chronic liver disease and hepatocellular carcinoma. Combination therapy with Interferon (peg-IFN-α) and Ribavirin (RBV) clear the virus more likely than the others. Different factors like virus and host characteristics influence on response to treatment. The most important viral factors include virus genotype and viral load; host factors like genetic, gender, race, age, weight and liver enzymes are also important. Previous studies have shown that single nucleotide polymorphisms (SNPs) in IFNR genes can regulate and influence on treatment with IFN. The purpose of this study is to investigate the association between SNPs in IFN-α receptor (IFNAR1 & IFNAR2) genes among subjects affected with chronic hepatitis C, who have treated with IFN and RBV, and also relationship between HCV genotypes and response to combination antiviral therapy. Peripheral blood mononuclear cells (PBMCs) were taken from whole blood of 61 patients affected with chronic hepatitis C who were treated with IFN and Ribavirin. Then, DNA was extracted from PBMCs and quality of DNA was assessed with Nanodrop finally two SNPs [Ex4-30G>C] and [Ivs1-4640 G>A] of IFN receptor genes (IFNAR1 and IFNAR2) were measured by TaqMan Real-Time PCR in ABi Prism 7900 system. Also to confirm the response rate to therapy, RNA was extracted then RT PCR was performed and final product was studied with gel electrophoresis and UV spectroscopy. Statistical analysis was performed using SPSS version 18.0 for Windows. The analysis of results from TaqMan SNP Genotyping has been shown that two SNPs (Ex4-30G>C and Ivs1-4640 G>A) of IFNAR1 and IFNAR2 didn't show any relationship with response to combined therapy in subjects affected with chronic hepatitis C who have treated with peg-IFN-α and Ribavirin. 61 patients complete the treatment period. 54 patients (%88/5) of them responded to treatment and 7 patients (%11/5) did not. Research and data analysis have shown that there is no significant relationship between sex (P=0 /7) and age (P=0 /2). But there is a relationship between genotype-3a and response to combined therapy of IFN-α and RBV (0/02). Studies have shown that gene polymorphisms in IVSS1-22G location of IFNAR1 gene had a relationship with IFN treatment response. But current study has shown that there is no significant relationship between two SNPs Ex4-30G>C and Ivs1-4640 G>A and response to IFN therapy. In continue we suggest that it would be better to use this technique to evaluate other SNPs in IFN genes.
authors.affiliation: Digestive Oncology Research Center Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran. shahzamani.k@lu.ac.ir.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Heidari
authors.affiliation: Department of Biology, Faculty of Sciences, Lorestan University, Khorram-abad, Iran. shahzamani.k@lu.ac.ir.
authors.forename: Kiana
authors.initials: K
authors.lastname: Shahzamani
authors.affiliation: Digestive Oncology Research Center Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran. shahzamani.k@lu.ac.ir.
authors.forename: Reza
authors.initials: R
authors.lastname: Ghanbari
authors.affiliation: Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran. shahzamani.k@lu.ac.ir.
authors.forename: Arash
authors.initials: A
authors.lastname: Tahamsebifar
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D017471:Receptors, Interferon / Q000235:genetics*; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D017471:Receptors, Interferon; D011092:Polyethylene Glycols; D012254:Ribavirin; D004247:DNA