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Erythropoietin-producing human hepatocellular carcino- ma receptor B1 (EPHB1) is a member of the Eph family of receptor tyrosine kinases that mediate vascular sys- tem development. Eph receptor overexpression has been observed in various cancers and is related to the malignant transformation, metastasis, and differentiation of cancers, including hepatocellular carcinoma (HCC). Eph receptors regulate cell migration and attachment to the extracellular matrix by modulating integrin activity. EphrinB1, the ligand of EPHB1, has been shown to reg- ulate HCC carcinogenesis. Here, we sought to de- termine whether EPHB1 polymorphisms are associated with hepatitis B virus (HBV)-infected liver diseases, in- cluding chronic liver disease (CLD) and HCC. We geno- typed 26 EPHB1 single nucleotide polymorphisms (SNPs) in 399 Korean CLD, HCC, and LD (CLD+HCC) cases and seroconverted controls (HBV clearance, CLE) using the GoldenGate assay. Two SNPs (rs6793828 and rs11717042) and 1 haplotype that were composed of these SNPs were associated with an increased risk for CLD, HCC, and LD (CLD+HCC) compared with CLE. Haplotypes that could be associated with HBV-infected liver diseases by affecting downstream signaling were located in the Eph tyrosine kinase domain of EPHB1. Therefore, we suggest that EPHB1 SNPs, haplotypes, and diplotypes may be genetic markers for the pro- gression of HBV-associated acute hepatitis to CLD and HCC.

genomics and informatics/genomics and informatics

Erythropoietin-producing Human Hepatocellular Carcinoma Receptor B1 Polymorphisms are Associated with HBV-infected Chronic Liver Disease and Hepatocellular Carcinoma in a Korean Population