Investigation of Transforming Growth Factor-β1 Gene Polymorphisms Among Iranian Patients With Chronic Hepatitis C

Abstract

BackgroundChronic hepatitis C infection is caused by the hepatitis C virus (HCV), and its clinical complications include liver cirrhosis, liver failure, and hepatocellular carcinoma.Transforming growth factor-β1 (TGF-β1) is an important cytokine in cell growthand differentiation, angiogenesis, extracellular matrix formation, immune responseregulation, and cancer development and progression.ObjectivesThe aim of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in TGF-β1 and chronic HCV infection among patients referred to the Taleghani Hospital, Tehran, Iran between 2008 and 2010.Patients and MethodsIn this case-control study, samples were collected using a convenience sampling method. We genotyped 164 HCV patients and 169 healthy controls for 3 SNPs in the TGF-β1 gene (-509 promoter, codon 10, and codon 25). We determined the SNP genotypes by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. To confirm the PCR-RFLP genotyping results, 10% of the samples were re-genotyped using a direct sequencing method.ResultsThere were no significant differences in the allelic frequency distribution of SNPs at -509 C/T, +869 C/T, or +915 G/C between HCV patients and the healthy controls. Genotyping results for all three polymorphic sites were similar with no statistically significant differences between the groups.ConclusionsMost of the Iranian patients (over 85%), both healthy controls and HCV patients, had the GG genotype at the +915 G/C position, resulting in a high level of TGF-β1 production. Therefore, we concluded that the SNPs investigated by us cannot be considered as prognostic factors for HCV infection in our population, despite being reported as prognostic markers in other populations. Moreover, there is a possibility that most of the population is susceptible to HCV infection.

Lack of Association Between Transforming Growth Factor Beta 1-509C/T and +915G/C Polymorphisms and Chronic Hepatitis B in Iranian Patients

“…Recently, Romani et al (2011) analyzed a possible link between +915G/C, -509C/T, +869T/C polymorphisms and chronic HCV infection in Iranian population. They could not find any association between studied factors ( 21 ).…”

Association of cytokine gene polymorphisms with hepatitis C virus infection in a population from Rio de Janeiro, Brazil

“… 41 Recently, Ramos et al, 29 in addition to examining an association with IL-28B polymorphisms, reported the participation of IL-10 (−1082) GG and IL-4 (+3) CT genotypes during acute hepatitis C with viral clearance. We failed to find an association with these cytokines, but the controversy regarding cytokine polymorphisms and CHC 42 – 44 encourages us to continue studying the influence of host polymorphisms and hepatitis C outcomes. Recently in a similar article, Pasha et al 45 reported that IL-28B, TGF-β1 (−509), and TNF-α (−308) polymorphisms that appear to influence cytokine production may be host genetic factors associated with HCV genotype 4 infection susceptibility and response to combined antiviral treatment, demonstrating the importance of host genetic factors in HCV infection outcome.…”

“…Romani et al concluded that SNPs in the TGF-β1 gene cannot be used as prognostic factors for HCV infection in an Iranian population, despite the possibility that most of the population is susceptible to HCV infection. 44 However, the functionally relevant TGF-β1 polymorphism (GG) at codon 25 may play a role in the rapid development of HCV-induced graft fibrosis, and the presence of the C allele in addition to younger donor age, female sex of the recipient, and HCV genotype other than 1b seems to protect against the development of advanced stages of fibrosis. 50 …”

TGF-β1 gene −509C>T promoter polymorphism modulates TGF-β1 levels in hepatitis E patients

“…In a different tune, Kimura et al have demonstrated − 509C allele to be associated with a higher clearance rate of HCV as well as with lower promoter activity ( Kimura et al, 2006 ). However, in the contest of hepatitis B and Iranian patients, absence of association between TGF-β1 − 509C > T and + 915G > C polymorphisms with chronic hepatitis B indicated that these changes do not play a significant role in increasing the risk of chronic infection in Iranian patients ( Razavi et al, 2014; Romani et al, 2011 ). Our finding of TGF-β1 polymorphism at position − 509 with increase in C > T genotype in the patient group suggests its protective role, since all the patients recovered.…”

“…Genotyping of the 3 SNPs in the TGF-β1 gene (− 509C > T, + 869T > C and + 915G > C) reported to be associated with alteration in plasma TGF-β1 levels ( Fig. 1 a) was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method ( Romani et al, 2011 ).…”