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

Kim,  Kyoung Yeon; Lee,  Seung Ku; Kim,  Min Ho; Cheong,  Jae Youn; Cho,  Sung Won; Yang,  Kap Seok; Kwack,  KyuBum

doi:2008.6.4.192

Genomics Inform > Volume 6(4); 2008 > Article

Original Article

Genomics & Informatics 2008;6(4): 192-201.

DOI: https://doi.org/10.5808/gi.2008.6.4.192

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

Kyoung Yeon Kim, Seung Ku Lee, Min Ho Kim, Jae Youn Cheong, Sung Won Cho, Kap Seok Yang, KyuBum Kwack

¹Medical Genomics Laboratory, Graduate School of Life Science and Biotechnology, Pochon CHA University, Seongnam 463-836, Korea. kbkwack@cha.ac.kr, kbkwack@gmail.com
²Department of Gastroenterology, Genomic Research Center for Gastroenterology, Ajou University School of Medicine, Suwon 442-721, Korea.
³Macrogen Inc. 60-24, Gasan-dong, Gumcheon-gu, Seoul 153-781, Korea.

Abstract

Erythropoietin-producing human hepatocellular carcinoma receptor B1 (EPHB1) is a member of the Eph family of receptor tyrosine kinases that mediate vascular system 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 regulate HCC carcinogenesis. Here, we sought to determine whether EPHB1 polymorphisms are associated with hepatitis B virus (HBV)-infected liver diseases, including chronic liver disease (CLD) and HCC. We genotyped 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 progression of HBV-associated acute hepatitis to CLD and HCC.

Keywords: chronic liver disease; hepatocellular carcinoma; Eph receptor; angiogenesis; polymorphism