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Association of IL28B SNPs rs12979860 and rs8099917 on Hepatitis C Virus-RNA Status in Donors/Recipients of Living Donor Liver Transplantation.

ABSTRACT: To investigate the effect of IL28B single nucleotide polymorphisms (SNPs) (rs8099917 and rs12979860) in the donors and recipients on the outcome of Hepatitis C virus-RNA clearance after living donor liver transplantation (LDLT). The rs8099917 and rs12979860 genotypes in 50 donor and recipients pairs were explored on the pre-operative day (POD) and post-operative day 30 (POD30). There was a significant difference in HCV-RNA clearance before (12%, 6/50) and after (48%, 24/50) liver transplantation (P < 0.001). The rs8099917 genotype TT was dominant in both the recipients (82%, 41/50) and donors (86%, 43/50), but had no significant effect on HCV-RNA clearance (87.5%, 21/24) and recurrence (76.9%, 20/26) after LDLT. One recipient was detected with genotype GG on POD, which changed to genotype GT on POD30. Prevalence of rs12979860 genotype CT was 98% (49/50 recipient) and 92% (46/50 donor) and prevalence of genotype CC was 2% (1/50 recipient) and 8% (4/50 donor) on POD and POD30, respectively. Of the 4 recipients with rs12979860 genotype CC on POD30, 3 recipients (12.5%, 3/24) exhibited HCV clearance and 1 experienced recurrence (3.9%, 1/26), however, this was not statistically significant. In conclusion, alterations in IL28B SNP genotype may occur after LDLT, leading to modifications in the host genome or donor proteome by HCV. This predicted mechanism will need to be investigated further.

SUBMITTER: Chiu KW

PROVIDER: S-EPMC4898820 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Association of IL28B SNPs rs12979860 and rs8099917 on Hepatitis C Virus-RNA Status in Donors/Recipients of Living Donor Liver Transplantation.

Chiu King-Wah KW Nakano Toshiaki T Chen Kuang-Den KD Lin Chih-Che CC Hu Tsung-Hui TH Goto Shigeru S Chen Chao-Long CL

PloS one 20160608 6

To investigate the effect of IL28B single nucleotide polymorphisms (SNPs) (rs8099917 and rs12979860) in the donors and recipients on the outcome of Hepatitis C virus-RNA clearance after living donor liver transplantation (LDLT). The rs8099917 and rs12979860 genotypes in 50 donor and recipients pairs were explored on the pre-operative day (POD) and post-operative day 30 (POD30). There was a significant difference in HCV-RNA clearance before (12%, 6/50) and after (48%, 24/50) liver transplantation ...[more]

PMID: 27275739

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Project description:Background and aimsGenetic polymorphisms near interleukin 28B gene are associated with spontaneous and treatment induced clearance of hepatitis C virus (HCV). Our objective was to evaluate the impact of interleukin 28B single nucleotide polymorphism (rs12979860, rs8099917) variability in HCV genotype 3 infected populations.Methods400 hepatitis C seroreactive patients from different population groups in Eastern and North Eastern part of India were assessed for host and viral genotypic analysis. 83 HCV genotype 3 infected patients were administered pegylated interferon- ribavirin therapy. Viral genotyping was performed using nested reverse transcriptase-PCR followed by direct sequencing methods. Host interleukin 28B genotyping was performed using real-time PCR based single nucleotide polymorphism analysis.ResultsOut of 400 hepatitis C seroreactive individuals, 73.25% were found to be RNA positive. HCV genotype 3 (65.87%) was found to be the major circulating strain in this region followed by genotype 1 (32.08%). rs12979860 CC genotype was significantly associated with sustained virological response in HCV genotype 3 infected population. In patients achieving rapid virological response, favourable CC/TT allele at rs12979860, rs8099917 was found to be predominant at both the alleles at 77%, 73.2% respectively; whereas in case of patients with relapsed HCV infection CT, TG alleles were found to be predominant. Additionally, CC genotypes at rs12979860 were found to be associated with sustained virological response in patients with high viral load (OR = 6.75, 0.05<p). HCV unfavourable rs12979860 TT, rs8099917 GG alleles were present in 34%, 27.6% patients with relapsed HCV infection respectively. Also unfavourable CT, TG genotypes were found to be predominant in patients with advanced stages of liver disease.ConclusionCC, TT the two favourable markers at SNPs rs12979860 and rs8099917 are strongly associated with sustained virological response in genotype 3 infected populations. This information will aid clinicians to effectively design response based treatment regimen.

Project description:BackgroundHost single-nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) locus are associated with sustained virological response to antiviral therapy and with spontaneous Hepatitis C Virus (HCV) clearance. Prevalence of these SNPs varies depending on ethnicity. The impact of IL28B SNPs in HCV-infected patients is currently unknown in Uruguay. Therefore, the aim of this study was to evaluate and compare the distribution of polymorphisms in the IL28B gene (rs12979860 and rs8099917) among HCV-infected patients and healthy individuals in Uruguay and thus assess their possible association with the establishment of HCV infection.MethodsDNA was recovered from 92 non-infected individuals and 78 HCV-infected patients and SNPs were determined by RFLP and allelic discrimination by real-time PCR.ResultsThe distribution of rs12979860 genotypes for the infected population was 29.5%-CC, 47.4%-CT and 23.1%-TT and for the control group 45.7%, 42.4% and 11.9%, respectively. Prevalence in both infected and uninfected individuals is similar to that reported in other countries with admixed populations. The distribution of rs8099917 genotypes for the infected population was 57.7%-TT, 27.2%-TG and 14.1%-GG and for the control group 60.9%, 33.7% and 5.4%, respectively. The comparison of rs12979860 genotype distribution between the two populations evidenced a higher prevalence of the favourable genotype (CC) in the uninfected control group (p < 0.05). Additionally, results generated using logistic regression analysis show that individuals carrying rs12979860-TT or CT genotypes have a higher likelihood of developing chronic hepatitis upon infection with HCV, when compared to CC carriers, considering rs8099917 genotype as constant.ConclusionPatients with HCV infection have a statistically significant lower prevalence of the favourable rs12979860 genotype when compared to uninfected individuals; therefore we can establish that only IL28B rs12979860-CT and TT genotypes seem to contribute to the occurrence of chronic HCV infection in the cohort of Uruguayan population studied. Considering that a trend towards a higher frequency of "good" response genotypes was observed in responder patients, we believe that IL28B rs12979860 genotyping could be a useful tool for predicting different therapies outcome, including in the DAA era.

Dataset Information

Association of IL28B SNPs rs12979860 and rs8099917 on Hepatitis C Virus-RNA Status in Donors/Recipients of Living Donor Liver Transplantation.

Publications

Association of IL28B SNPs rs12979860 and rs8099917 on Hepatitis C Virus-RNA Status in Donors/Recipients of Living Donor Liver Transplantation.

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