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Background and study aims
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.Patients and methods
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.Results
Two functional SNPs were detected: rs62133148T>G and rs12992188C>T 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).Conclusion
This study is a pioneer clinical study on these two functional SNPs (rs62133148T>G and rs12992188 C>T). 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. 相似文献Methods: A total of 102 patients were divided into two groups: Radical liver resection only (LR group, 52 patients) and radical liver resection combined with post-operative TACE (combined group, 50 patients). Survival analysis was performed using the Kaplan–Meier method. Univariate and multivariate analysis were performed using Cox proportional analysis to detect prognostic factors of survival outcomes.
Results: The 1-, 3- and 5-year survival rate in the LR group were significantly lower compared with those in combined group (p?=?.019). The 1-, 3- and 5-year progression-free survival rate in the LR group were also lower than those in the combined group (p?=?.048). Multivariate analysis detected that tumor number (multiple vs single), tumor distribution (both lobes vs semi-liver), treatment strategy (surgery?+?TACE vs surgery) were independent factors for OS (HR values were 2.307, 3.155 and 0.526, respectively) and PFS (HR values were 1.938, 3.425 and 0.633, respectively; p?<?.05).
Conclusion: In conclusion, surgery combined with post-operative TACE may improve survival outcomes for patients with intermediate HCC. Tumor number, tumor distribution and treatment strategy (surgery?+?TACE) were significantly associated with the prognosis of patients with intermediate HCC. 相似文献