Impact of TGF-ß1 Gene Polymorphism (rs1800469) on Treatment Response to Pegylated Interferon/Ribavirin in Iranian Patients with Hepatitis C.

BACKGROUND: Hepatitis C virus as a major cause of chronic liver disease affects more than 170 million people worldwide. Recent studies have claimed that single nucleotide polymorphisms (SNPs) for the transforming growth factor-ß1 (TGF-ß1) gene were strongly associated with the antiviral treatment response. Thus, the present study aimed at the determination of distribution of the rs1800469 (C/T) polymorphism among Iranian with chronic hepatitis C. METHODS: A total of 165 blood samples including 68 SVR positive and 21 non-responder samples from individuals suffering chronic hepatitis C and also 76 healthy individual controls were analyzed in this cross-sectional study. DNA was isolated from the samples using a DNA extraction standard kit. Then the frequency of the polymorphism was analyzed using PCR-RFLP method. Eventually, the products of interest were detected on 2.5% agarose gel electrophoresis. RESULTS: The distribution of the C/T polymorphism between healthy individuals and patients were obtained as TT: 22.4%, TC: 46%, CC: 31.6%, and TT: 19.1%, TC: 48.3%, CC: 32.6%, respectively. Furthermore, the CC genotype was identified in 20 patients of whom 68 achieved SVR, while the CT heterozygous was found in 43 patients and SVR was achieved in 38. Finally, the TT was detected in 17 patients, and 7 patients did not achieve SVR. CONCLUSIONS: We observed a significant difference of C allele frequency with SVR as compared to the T allele among patients (p = 0.064). On the other hand, there is no correlation between the polymorphism and susceptibility to HCV infection. However, further studies with more samples seem to be necessary.

Correlation Study Between IL-28B Gene Polymorphism (rs8099917SNP) and Sustained Virological Response in Iranian Patients with Chronic Hepatitis C.

BACKGROUND: The current standard treatment for hepatitis C is a combination of pegylated interferon alpha and ribavirin (peg-IFNα/RBV). Recent studies have shown that single nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) gene coding for IFN-λ3 were associated with the antiviral treatment response. Therefore, in this study, we determined the distribution of the rs8099917 (T/G) polymorphism with sustained virological response (SVR) to chronic hepatitis C virus infection among Iranian patients. METHODS: This cross-sectional study was performed on 150 blood samples based on 93 patients with chronic HCV genotypes 1 and 3 including 71 SVR positive, 22 negative, and 57 healthy individual controls. DNA was extracted from the samples and the frequency of the polymorphism was analyzed the using PCR-RFLP method. Finally, the products were detected on 3.5% agarose gel electrophoresis. RESULTS: The analysis of the data for G/T polymorphism showed that the GG genotype was identified in 6 patients of 71 who achieved SVR, while the GT heterozygous was found in 33 patients and SVR was achieved in 19. Finally, the TT was detected in 53 patients and 7 patients were resistant to treatment. CONCLUSIONS: The results showed significant effects of G allele carriers on susceptibility to HCV infection com-pared to the other allele (T) in our studied population (p = 0.013, OR = 2.23, 95% CI = 1.18-4.21), but we did not find a significant correlation for SVR to therapy in patients with genotype TT (p = 0.055, OR = 0.48, 95% CI = 0.23-1.01). However, further studies with more samples are necessary.

Role of IL28-B Polymorphism (rs12979860) on Sustained Virological Response to Pegylated Interferon/Ribavirin in Iranian Patients With Chronic Hepatitis C.

BACKGROUND: The current medical treatment for hepatitis C virus (HCV) infection is pegylated interferon plus ribavirin, but just 50% of genotype 1 HCV patients and about 80% of HCV genotype 3 patients are treated completely. Recently, the rs12979860 C/T polymorphism, which is located 3 kb upstream of the IL28b gene that codes IFNλ3, shows a powerful association in response to the treatment in HCV patients. OBJECTIVES: The aim of this study was to evaluate the relationship between IL28b single nucleotide polymorphism (SNP) and treatment outcomes among chronic HCV patients in Iran. PATIENTS AND METHODS: In this cross-sectional study, 108 blood samples were collected from chronic patients in Iran; 50 unrelated healthy subject samples were also collected. Genomic DNA was extracted, and rs12979860 SNP was done by PCR-RFLP. Finally, products were detected on 12% polyacrylamide gel electrophoresis. RESULTS: The analysis of data for C/T SNP showed that the CC genotype is more common in the control group than in the group of patients. In contrast, the frequency of TT as a mutant genotype is more frequent in patients than in uninfected people. In addition, results showed a statistically significant relationship between CC, CT, and TT genotypes in sensitive and resistant groups (P value: < 0.001, Or: 0.003, CI: 0-0.047). This relationship was also examined in terms of allele frequency, to determine whether the possibility of resistance to treatment in patients with T allele is more than in patients who carry C allele (P value: < 0.001). CONCLUSIONS: These results showed a significant effect between rs12979860 SNP and sustained virological response (SVR) rate in Iranian patients with chronic HCV. To decrease the cost of long treatments and to prevent severe side effects, determining this polymorphism at the beginning of treatment can be very helpful for patients and physicians.