4.7 Article

Association of common promoter polymorphisms of MCP1 wth hepatitis B virus clearance

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EXPERIMENTAL AND MOLECULAR MEDICINE
卷 38, 期 6, 页码 694-702

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NATURE PUBLISHING GROUP
DOI: 10.1038/emm.2006.82

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angiotensinogen; cadherins; cyclooxygenase-2; carcinoma, hepatocellular; chemokine CCL2; hepatitis B virus; P-glycoprotein; polymorphism, single nucleotide; RANTES; thrombospondins

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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 (MCPI), 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 con trolling 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 (117.7% 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.

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