Kim Lyoung Hyo, Cheong Hyun Sub, Namgoong Suhg, Kim Ji On, Kim Jeong-Hyun, Park Byung Lae, Cho Sung Won, Park Neung Hwa, Cheong Jae Youn, Koh InSong, Shin Hyoung Doo, Kim Yoon-Jun
Department of Life Science, Sogang University, Republic of Korea; Department of Genetic Epidemiology, SNP Genetics, Inc., Republic of Korea.
Department of Genetic Epidemiology, SNP Genetics, Inc., Republic of Korea.
Infect Genet Evol. 2015 Jul;33:72-6. doi: 10.1016/j.meegid.2015.04.013. Epub 2015 Apr 22.
A recent genome-wide association study (GWAS) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) identified two loci (rs7574865 in STAT4 and rs9275319 in HLA-DQ) in a Chinese population. We attempted to replicate the associations between the two SNP loci and the risk of HCC in a Korean population. The rs7574865 in STAT4 and rs9275319 in HLA-DQ were genotyped in a total of 3838 Korean subjects composed of 287 HBV-related hepatocellular carcinoma patients, 671 chronic hepatitis B virus (CHB) patients, and 2880 population controls using TaqMan genotyping assay. Gene expression was measured by microarray. A logistic regression analysis revealed that rs7574865 in STAT4 and rs9275319 in HLA-DQ were associated with the risk of CHB (OR = 1.25, P = 0.0002 and OR = 1.57, P= 1.44 × 10(-10), respectively). However, these loci were no association with the risk of HBV-related HCC among CHB patients. In the gene expression analyses, although no significant differences in mRNA expression of nearby genes according to genotypes were detected, a significantly decreased mRNA expression in HCC subjects was observed in STAT4, HLA-DQA1, and HLA-DQB1. Although the genetic effects of two HCC susceptibility loci were not replicated, the two loci were found to exert susceptibility effects on the risk of CHB in a Korean population. In addition, the decreased mRNA expression of STAT4, HLA-DQA1, and HLA-DQB1 in HCC tissue might provide a clue to understanding their role in the progression to HCC.
最近一项针对乙肝病毒（HBV）相关肝细胞癌（HCC）的全基因组关联研究（GWAS）在中国人群中确定了两个基因座（STAT4中的rs7574865和HLA-DQ中的rs9275319）。我们试图在韩国人群中复制这两个单核苷酸多态性（SNP）基因座与HCC风险之间的关联。使用TaqMan基因分型检测法，对总共3838名韩国受试者（包括287名HBV相关肝细胞癌患者、671名慢性乙肝病毒（CHB）患者和2880名群体对照）的STAT4中的rs7574865和HLA-DQ中的rs9275319进行了基因分型。通过微阵列测量基因表达。逻辑回归分析显示，STAT4中的rs7574865和HLA-DQ中的rs9275319与CHB风险相关（优势比（OR）分别为1.25，P = 0.0002和OR = 1.57，P = 1.44×10^(-10)）。然而，这些基因座与CHB患者中HBV相关HCC的风险无关。在基因表达分析中，虽然未检测到根据基因型在附近基因的mRNA表达上有显著差异，但在HCC受试者中观察到STAT4、HLA-DQA1和HLA-DQB1的mRNA表达显著降低。尽管未能复制两个HCC易感基因座的遗传效应，但发现这两个基因座对韩国人群中CHB的风险有易感作用。此外，HCC组织中STAT4、HLA-DQA1和HLA-DQB1的mRNA表达降低可能为理解它们在进展为HCC中的作用提供线索。
