Park Byung Lae, Kim Yoon Jun, Cheong Hyun Sub, Kim Lyoung Hyo, Choi Yoo Hyun, Lee Hyo-Suk, Shin Hyoung Doo
Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul 153-803, Korea.
Exp Mol Med. 2006 Dec 31;38(6):694-702. doi: 10.1038/emm.2006.82.
Hepatocellular carcinoma (HCC) is one of the most common malignant cancers closely associated with chronic infection by the hepatitis B virus (HBV) or the hepatitis C virus (HCV) throughout the world. In this study, the genetic associations of 20 known polymorphisms in eight candidate genes, including angiotensinogen (AGT), cadherin 1 (CDH1), cyclooxygenase 2 (COX2), monocyte chemotactic protein-1 (MCP1), multidrug resistance 1 (MDR1), chemokine ligand 5 (RANTES), thrombospondin 2 (THBS2), and thrombospondin 4 (THBS4), were analyzed in a large chronic hepatitis B cohort (n=1,095) recruited from the Korean population. In addition, three polymorphisms in chemokine receptor 4 (CXCR4) and vimentin (VIM) identified in this study were also genotyped. Using logistic regression analysis controlling possible confounding factors, one common (freq.=0.367) promoter polymorphism of MCP1 (MCP1-2518G>A) among analyzed polymorphisms was significantly associated with clearance of HBV infection. The frequency of homozygotes for the MCP1-2518A allele (MCP1-2518A/A) among chronic hepatitis B virus (HBV) carrier patients was significantly higher than that among spontaneously recovered (SR) subjects (17.7% vs. 10.4%)(OR=1.78, P=0.004). Our findings imply a plausible explanation for the contribution of host genetic determinants to the variable outcome of HBV infection, which might provide valuable information for future genetic study in this area.
肝细胞癌(HCC)是全球最常见的恶性肿瘤之一,与乙型肝炎病毒(HBV)或丙型肝炎病毒(HCV)的慢性感染密切相关。在本研究中,我们对来自韩国人群的一个大型慢性乙型肝炎队列(n = 1,095)进行了分析,研究了8个候选基因(包括血管紧张素原(AGT)、钙黏蛋白1(CDH1)、环氧化酶2(COX2)、单核细胞趋化蛋白-1(MCP1)、多药耐药蛋白1(MDR1)、趋化因子配体5(RANTES)、血小板反应蛋白2(THBS2)和血小板反应蛋白4(THBS4))中20个已知多态性的遗传关联。此外,我们还对本研究中鉴定出的趋化因子受体4(CXCR4)和波形蛋白(VIM)中的3个多态性进行了基因分型。通过控制可能的混杂因素进行逻辑回归分析,在所分析的多态性中,MCP1的一种常见(频率 = 0.367)启动子多态性(MCP1 - 2518G>A)与HBV感染的清除显著相关。慢性乙型肝炎病毒(HBV)携带者患者中MCP1 - 2518A等位基因(MCP1 - 2518A/A)纯合子的频率显著高于自发恢复(SR)受试者(17.7%对10.4%)(OR = 1.78,P = 0.004)。我们的研究结果为宿主遗传决定因素对HBV感染可变结局的作用提供了一个合理的解释,这可能为该领域未来的基因研究提供有价值的信息。