Association of 49245A>G (rs868) Polymorphism in the 3’UTR of Donor TGFBR1 Gene with Course of Hepatitis C following Orthotopic Liver Transplantation

Abstract

Clinical course of hepatitis C after OLT may depend on donor rs868 SNP located in TGFBR1 3'UTR.

Negative Correlation Between Hepatitis C Virus (HCV) and Let-7 MicroRNA Family in Transplanted Livers: The Role of rs868 Single-Nucleotide Polymorphism

“…rs868 was also influential at the clinical level. The comparison of the pathological data revealed an apparent and significant negative correlation between let-7 miRNA expression and inflammation score (Ishak A) in the AG genotype carriers for rs868, consistent with the previously reported better clinical outcome of this genotype in comparison to AA genotype ( Table 4 ) [ 18 ]. Ishak A score is a semiquantitative measure of periportal or periseptal interface hepatitis (piecemeal necrosis)[ 26 ].…”

“…In our study, we demonstrated a strong negative correlation between let-7/miR-98 miRNA family members and TGFBR1 mRNA ( Table 2 ). Again, it was more prominent and reached statistical significance in the AG genotype carriers for rs868, the same genotype that was advantageous in our previous study in terms of hepatitis C recurrence severity [ 18 ].…”

“…The clinical effect of polymorphisms located in the let-7 complementary binding site has been previously demonstrated for an SNP located in the 3′UTR region of the KRAS gene in non-small cell lung cancer [ 37 ]. In our previous study, we showed that HCV-infected liver transplant recipients carrying the rs868 AG genotype have a more favorable outcome in comparison to the AA genotype carriers in terms of severity of hepatitis C recurrence [ 18 ]. Recently, the clinical effect of rs868 has been also demonstrated in hereditary mismatch repair-proficient colorectal cancer (MSS HNPCC), where the A allele was a risk-associated genotype, proving the potential of this SNP for modification of the course of diseases [ 38 ].…”

“…Single-nucleotide polymorphisms (SNPs) located in 3′UTR have been described in numerous studies to alter this interaction, with a significant clinical effect [ 15 – 17 ]. In our previously published study, we found an association between the severity of hepatitis C recurrence after LT and rs868 SNP genotype of the donor liver, with the AG genotype carriers presenting a significantly more favorable outcome over the AA genotype carriers [ 18 ]. Rs868 is located in the 3′UTR region of TGF-β receptor type 1 gene ( TGFBR1 ).…”

The Variant at TGFBRAP1 but Not TGFBR2 Is Associated with Antituberculosis Drug-Induced Liver Injury

“…The mutant form of TGFBRAP1 may inhibit the signalling pathway through interference complex formation [10]. Therefore, as the important role of TGFBRAP1 and TGFBR2 in the signalling pathway, genetic gene polymorphisms of TGFBRAP1 and TGFBR2 have been researched in hepatocellular carcinomas and hepatitis C infection, which indicated that genetic polymorphisms of TGFBRAP1 and TGFBR2 may disturb the regulation in liver injury and renewal [11–13]. However, to the best of our knowledge, no genetic associations between TGFBRAP1 and TGFBR2 variants and ATDILI have been reported.…”