Hepatitis B virus mutations, expression quantitative trait loci for PTPN12, and their interactions in hepatocellular carcinoma.
Hepatitis B virus mutations, expression quantitative trait loci for PTPN12, and their interactions in hepatocellular carcinoma.
复制标题
乙型肝炎病毒突变、PTPN12表达数量性状位点及其在肝细胞癌中的相互作用
作者：
Song C;Liu Y;Xu L;Wen J;Jiang D;Chen J;Zhai X;Hu Z;Liu L;Liu J
以前我们发现HBV（Hepatitis B virus）序列变异可能与宿主人类白细胞抗原（human leukocyte antigen，HLA）基因变异相互作用，影响宿主发生肝细胞癌（hepatocellular carcinoma，HCC）的风险。需要确定更多的HBV-宿主相互作用。蛋白酪氨酸磷酸酶非受体12（PTPN 12）作为酪氨酸激酶信号通路的拮抗剂，可能在抗HBV感染的免疫应答和HCC的发生发展中起重要作用。经生物信息学分析，Rs 11485985为PTPN 12的一个表达数量性状位点（eQTL）。在这项研究中，我们在病例对照队列中对PTPN 12 eQTL进行基因分型，并对HBV区域EnhII/BCP/PC进行测序，该队列包括1507例HBV相关HCC病例和1560例HBV持续携带者作为对照。与HBV持续携带者相比，rs 11489585的变异基因型GG增加了HCC的风险（校正OR = 2.03，95%置信区间[CI] = 1.30-3.18）。我们还检测到PTPN 12 eQTL rs 11489585与HBV突变的边缘显著相关性（G1799 C的P = 0.05）。总之，PTPN 12可能影响伴随HBV突变的HCC风险。
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.