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Association of interleukin-28B polymorphisms with platelet count and liver function recovery after liver transplant.

ABSTRACT: The present genome-wide association study investigated the relationship of interleukin 28B (IL-28B) genetic variants with HBV susceptibility and prognosis of HBV-infected patients. This study aims to examine the role of IL-28B polymorphisms on transplant etiologies and the liver function recovery in Chinese liver transplant recipients.A total of 231 liver transplant recipients were enrolled in the study. The transplant etiologies included progressive HBV hepatitis, HBV-related liver cirrhosis (LC), HBV-related hepatocellular carcinoma (HCC), and non-HBV-related disease. All recipients were in stable condition before transplantation. Three single nucleotide polymorphisms (SNPs) of IL-28B (rs12979860, rs12980275, rs8099917) of recipients were analyzed by high-resolution melting (HRM) curve analysis. Liver function, blood cell count, and coagulation function were regularly tested before and for next 5 years after transplantation.No significant association was found between IL-28B gene polymorphisms and transplant etiologies. Peripheral platelet count in the third and fourth days after transplantation were significantly higher in recipients carrying IL-28B rs12979860 T allele, or rs8099917 C allele (P?

SUBMITTER: Li Y

PROVIDER: S-EPMC5682771 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Association of interleukin-28B polymorphisms with platelet count and liver function recovery after liver transplant.

Li Yi Y Wei Tiantian T Yan Lin L Yang Zhiqiang Z Huang Qian Q Shi Yunying Y Wang Lanlan L

Medicine 20171101 44

The present genome-wide association study investigated the relationship of interleukin 28B (IL-28B) genetic variants with HBV susceptibility and prognosis of HBV-infected patients. This study aims to examine the role of IL-28B polymorphisms on transplant etiologies and the liver function recovery in Chinese liver transplant recipients.A total of 231 liver transplant recipients were enrolled in the study. The transplant etiologies included progressive HBV hepatitis, HBV-related liver cirrhosis (L ...[more]

PMID: 29095252

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Project description:AIM:To analyze the role of rs12979860 and rs8099917 polymorphisms in hepatitis C virus (HCV) genotype 1 infection of Brazilians. METHODS:A total of 145 adult patients diagnosed with genotype 1 chronic hepatitis C (CHC) who had completed a 48-wk regimen of pegylated-interferon ?-2a or -2b plus ribavirin combination therapy were recruited from six large urban healthcare centers and 199 healthy blood donors (controls) from a single site between January 2010 and January 2012. Data on the patients' response to treatment was collected. Polymerase chain reaction-restriction fragment length polymorphism genotyping of the interleukin (IL)28B gene fragment encompassing the single nucleotide polymorphisms (SNPs) rs12979860 (C/T) and rs8099917 (T/G) was carried out for 79 of the CHC patients and 199 of the controls. Bi-directional amplicon sequencing of the two SNPs was carried out for the remaining 66 CHC patients. RESULTS:SNP rs12979860 genotyping was successful in 99.5% of the controls and 97.2% of the CHC patients, whereas the SNP rs8099917 genotyping was successful in 95.5% of the controls and 100% of the CHC patients. The genotype and allele distributions for both rs12979860 and rs8099917 were significantly different between the control and CHC patient groups, with significantly higher genotype frequencies of CC and TT in the controls (P = 0.037 and 0.046, respectively) and of TT and GG in the CHC patients (P = 0.0009 and 0.0001, respectively). Analysis of the CHC patients who achieved sustained virological response (SVR) to treatment (n = 55) indicated that the rs12979860 C allele and CC genotype were predictors of SVR (P = 0.02). No significant correlation was found between rs8099917 genotypes and treatment response, but carriers of the T allele showed significantly higher rates of SVR (P = 0.02). Linkage disequilibrium analysis of the group that achieved SVR showed a significant association between rs12979860 and rs8099917 (P = 0.07). CONCLUSION:The higher allele frequency of rs12979860 C and rs8099917 T observed in non-HCV-infected individuals may indicate a potential protective role for these IL28B-related polymorphisms.

Project description:BACKGROUND:Tacrolimus is the first-line immunosuppressant after organ transplantation. It is mainly metabolized by cytochrome P450, family 3, subfamily A (CYP3A) enzymes, but there are large individual differences in metabolism. Interleukin 6 (IL6) has been shown to cause a pan-suppression of mRNA levels of ten major CYP enzymes in human hepatocyte cultures. IL6 has been shown to provide hepatoprotection in various models of liver injury. Rs1800796 is a locus in the IL6 gene promoter region which regulates cytokine production. We speculated that IL6 rs1800796 polymorphisms may lead to individual differences in tacrolimus metabolism by affecting CYP3A enzymes levels and liver function after liver transplantation. METHODOLOGY/PRINCIPAL FINDINGS:Ninety-six liver transplant patients receiving tacrolimus were enrolled in the study. Two single nucleotide polymorphisms (SNP), CYP3A5 rs776746 and IL6 rs1800796, were genotyped in both donors and recipients. The effects of SNPs on tacrolimus concentration/dose (C/D ratio) at four weeks after transplantation were studied, as well as the effects of donor IL6 rs1800796 polymorphisms on liver function. Both donor and recipient CYP3A5 rs776746 allele A showed association with lower C/D ratios, while donor IL6 rs1800796 allele G showed an association with higher C/D ratios. Donor CYP3A5 rs776746 allele A, IL6 rs1800796 allele C, and recipient CYP3A5 rs776746 allele A were associated with fast tacrolimus metabolism. With increasing numbers of these alleles, patients were found to have increasingly lower tacrolimus C/D ratios at time points after transplantation. Donor IL6 rs1800796 allele G carriers showed an association with higher glutamic-pyruvic transaminase (GPT) levels. CONCLUSIONS:Combined analysis of donor CYP3A5 rs776746, IL6 rs1800796, and recipient CYP3A5 rs776746 polymorphisms may distinguish tacrolimus metabolism better than CYP3A5 rs776746 alone. IL6 may lead to individual differences in tacrolimus metabolism mainly by affecting liver function.

Dataset Information

Association of interleukin-28B polymorphisms with platelet count and liver function recovery after liver transplant.

Publications

Association of interleukin-28B polymorphisms with platelet count and liver function recovery after liver transplant.

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