Two novel SNPs in the promoter region of PKR gene in hepatitis C patients and their impact on disease outcome and response to treatment
| Autor: | Dina H. El-Dahshan, Amro Hanora, Doaa Bahy, Ahmed Wahid, Amr Ahmed |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male Genotype Sustained Virologic Response Single-nucleotide polymorphism Antiviral Agents Polymorphism Single Nucleotide 03 medical and health sciences chemistry.chemical_compound eIF-2 Kinase Interferon Ribavirin medicine Humans Treatment Failure Promoter Regions Genetic Gene Alleles business.industry Gastroenterology virus diseases Promoter Hepatitis C Middle Aged medicine.disease Protein kinase R Virology 030104 developmental biology chemistry Case-Control Studies Female Interferons business Nucleic Acid Amplification Techniques medicine.drug |
| Zdroj: | Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology. 19(3) |
| ISSN: | 2090-2387 |
| Popis: | The double-stranded RNA dependent protein kinase (PKR) plays a vital role in the immune system. During HCV infection, PKR has antiviral effect by inhibition of protein synthesis of the HCV. The functional single nucleotide polymorphisms (SNPs) in PKR promoter region might have a relation to HCV disease outcome and response to treatment. The objective of the present work was threefold. First, it proposed an optimized protocol for PCR amplification of PKR promoter. Second, it screened the promoter region of PKR gene in HCV Egyptian patients to detect the possible SNPs' function. Third, to study the association between the detected SNPs and the response to treatment.The functional SNPs in PKR promoter region were detected using DNA sequencing in 40 HCV infected patients; 20 sustained virologic response (SVR) patients and 20 nonresponse (NR) patients after combined interferon/ribavirin therapy. Twenty healthy subjects were included as a control.Two functional SNPs were detected: rs62133148TG and rs12992188CT within our target PKR promoter region. In rs62133148 polymorphism, there is a significant difference between patients and control subjects for TT and TG genotypes (p 0.0001). In addition, the G allele is more predominant in HCV patients. In rs12992188 polymorphism, the CC genotype is significantly different between patients and healthy control subjects (OR/95% CI: 0.033/0.006-0.172, p 0.0001). The presence of C allele was significantly associated with the NR patients (OR/95%CI: 0.25/0.097-0.643, p = 0.006). The TT genotype is significantly different between SVR and NR (OR/95%CI: 8.5/1.54-46.871, p = 0.014).This study is a pioneer clinical study on these two functional SNPs (rs62133148TG and rs12992188 CT). The rs62133148 polymorphism does not show any association with response to treatment. The TT genotype in rs12992188 polymorphism shows association with response to treatment. Therefore, patients with TT genotypes were more likely to achieve SVR. |
| Databáze: | OpenAIRE |
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