Dataset Information

Hepatitis B virus mutations, expression quantitative trait loci for PTPN12, and their interactions in hepatocellular carcinoma.

ABSTRACT: Previously we identified that HBV(Hepatitis B virus) sequence variation, which may interact with host human leukocyte antigen (HLA) genetic variation, could influence host risk of hepatocellular carcinoma (HCC). More HBV-host interactions need to be identified. Protein tyrosine phosphatase nonreceptor type 12 (PTPN12), serves as an antagonist to tyrosine kinase signaling, may play integral roles in immune response against HBV infection and the development of HCC. Rs11485985 was an expression quantitative trait loci (eQTL) for PTPN12 by bioinformatics analyses. In this study, we genotyped the PTPN12 eQTL and sequenced the HBV region EnhII/BCP/PC in a case-control cohort including 1507 HBV-related HCC cases and 1560 HBV persistent carriers as controls. The variant genotype GG of rs11489585 increased HCC risk compared to the HBV persistent carriers (adjusted OR = 2.03, 95% confidence interval [CIs] = 1.30-3.18). We also detected borderline significant associations of PTPN12 eQTL rs11489585 with HBV mutations (P = 0.05 for G1799C). Taken together, PTPN12 may influence HCC risk accompanied by HBV mutations.

SUBMITTER: Song C

PROVIDER: S-EPMC4944896 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hepatitis B virus mutations, expression quantitative trait loci for PTPN12, and their interactions in hepatocellular carcinoma.

Song Ci C Liu Yao Y Xu Lu L Wen Juan J Jiang Deke D Chen Jianguo J Zhai Xiangjun X Hu Zhibin Z Liu Li L Liu Jibin J

Cancer medicine 20160414 7

Previously we identified that HBV(Hepatitis B virus) sequence variation, which may interact with host human leukocyte antigen (HLA) genetic variation, could influence host risk of hepatocellular carcinoma (HCC). More HBV-host interactions need to be identified. Protein tyrosine phosphatase nonreceptor type 12 (PTPN12), serves as an antagonist to tyrosine kinase signaling, may play integral roles in immune response against HBV infection and the development of HCC. Rs11485985 was an expression qua ...[more]

PMID: 27075395

Similar Datasets

Project description:Genetic dissection of the S rat genome has provided strong evidence for the presence of two interacting blood pressure (BP) quantitative trait loci (QTLs), termed QTL1 and QTL2, on rat chromosome 5. However, the identities of the underlying interacting genetic factors remain unknown. Further experiments targeted to identify the interacting genetic factors by the substitution mapping approach alone are difficult because of the interdependency of natural recombinations to occur at the two QTLs. We hypothesized that the interacting genetic factors underlying these two QTLs may interact at the level of gene transcription and thereby represent expression QTLs (eQTLs). To detect these interacting eQTLs, a custom QTL chip containing the annotated genes within QTL1 and QTL2 was developed and used to conduct a transcriptional profiling study of S and two congenic strains that retain either one or both the QTLs. The results uncovered an interaction between two transcription factors, DMRTA2 and NFIA. Further, the âbiological signatureâ elicited by these two transcription factors was differential between the congenic strain that retained LEW alleles at both QTL1 and 2 compared to the congenic strain that retained LEW alleles at QTL1 alone. A network of transcription factors potentially affecting BP could be traced, lending support to our hypothesis. Pairs of Cy5 and Cy3 labeled targets were co-hybridized onto either a custom long oligonucleotide microarray for the interrogation of 231 genes encompassed by QTL1 and QTL2, or a TIGR rat cDNA array consisting of 26,401 probe elements representing 20,465 unique non-QTL genes. A âflip-dyeâ or âbalanced blockâ design was used as the experimental method of choice to account for potential dye-bias labeling effects. Six âbalanced blockâ normalized files are submitted for the long oligonucleotide array interrogating the hearts from S versus S.LEW(5)x6x9 animals, fourteen âflip-dyeâ hybridizations are submitted for the cDNA array interrogating the hearts from S versus S.LEW(5)x6x9 animals, and twelve âflip-dyeâ hybridizations are submitted for the cDNA array interrogating the hearts from S versus S.LEW(5)x6x11 animals. GPR and MEV files cannot be located.

Project description:AimTo investigate the relationship between hepatitis B virus (HBV) genotype with spontaneous YMDD mutations and hepatocellular carcinoma (HCC) in HBV-related cirrhosis.MethodsWe investigated 264 liver cirrhosis patients who were not treated with antiviral drugs, including 81 patients with HCC. YMDD mutations were detected by fluorescent hybridization bioprobe polymerase chain reaction (PCR) and melting curve assay using the Diagnosis Kit for HBV YMDD Mutation. Serum HBV genotypes were detected by real-time PCR using genotype-specific TaqMan probes. Statistical analysis was performed according to data type using the t test, χ(2) test and unconditional logistic regression analysis.ResultsIn the HCC group, genotype C strains, spontaneous YMDD mutations, and genotype C strains with YMDD mutations were detected in 33 (40.74%), 13 (16.05%) and 11 (13.58%) patients, respectively. In the liver cirrhosis (LC) group, HBV genotype C strains, spontaneous YMDD mutations, and genotype C strains with YMDD mutations were detected in 33 (18.03%), 7 (3.83%) and 2 (1.09%) patients, respectively. The differences in genotype C strains, spontaneous YMDD mutations, and genotype C strains with YMDD mutations between the two groups were statistically significant (χ(2) = 15.441, P = 0.000; χ(2) = 11.983, P = 0.001; P = 0.000). In the HCC and LC groups, there were seven patients infected by genotype B strains with YMDD mutations and 13 by genotype C strains with YMDD mutations. Further research revealed that HCC occurred in 2 patients infected by genotype B strains with YMDD mutations and 11 infected by genotype C strains with YMDD mutations. The difference was statistically significant (P = 0.000). Unconditional logistic regression analysis revealed that patients infected by genotype C strains with spontaneous YMDD mutations had a 7.775-fold higher risk for the development of HBV-related HCC than patients infected by other type HBV strains (P = 0.013, 95%CI: 1.540-39.264).ConclusionGenotype C strains with spontaneous YMDD mutations are an independent risk factor for HCC in LC patients and are important for early warning of HCC.

Dataset Information

Hepatitis B virus mutations, expression quantitative trait loci for PTPN12, and their interactions in hepatocellular carcinoma.

Publications

Hepatitis B virus mutations, expression quantitative trait loci for PTPN12, and their interactions in hepatocellular carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets