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.

Prognostic Value of Phosphotyrosine Phosphatases in Hepatocellular Carcinoma

“…1B, 3B, we got diametrically opposed results in term of PTPN12, which has been reported as a HBV associated protein [15, 21-23]. Moreover, the majority of patients from the TCGA cohort were at the risk of Hepatitis C, Nonalcoholic Fatty Liver Disease (NAFLD) or excessive alcohol consumption, while almost all patients of our validated cohort are Hepatitis B infectors.…”

“…It is rather remarkable that one of the expression quantitative trait loci (eQTL) for PTPN12 could multiplicatively interact with HBV hotspot mutation, which was suggested to significantly increase the risk of both chronic HBV infection and HBV-related HCC [21]. Moreover, PTPN12 inhibits secondary T-cell responses and is implicated in human autoimmunity, which may be either beneficial or detrimental to those infected with HBV [22, 23].…”

Long non‑coding RNAs in HBV‑related hepatocellular carcinoma (Review)

“…They are significantly enriched for disease-associated polymorphisms. Several SNPs in lncRNAs, such as rs7248320 (123), rs3757328 (124), rs6940552 (124,125), rs9261204 (124,125), rs11489585 (126), rs79037040 (127) and rs2055822 (127), are eQTLs for a series of genes and may contribute to the risk of HBV-related HCC. In addition to affecting the risk of HBV-related HCC, some eQTLs, such as rs1110839 (128) and rs4848320 (128), may affect the prognosis of HBV-related HCC.…”