Exp Mol Med.  2006 Dec;38(6):694-702.

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

Affiliations
  • 1Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul 153-803, Korea. hsleemd@snu.ac.kr
  • 2Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 110-744, Korea

Abstract

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.

Keyword

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

MeSH Terms

Promoter Regions (Genetics)/*genetics
Polymorphism, Genetic/*genetics
Middle Aged
Male
Humans
Hepatitis B virus/*physiology
Hepatitis B/complications/*genetics/therapy/*virology
Haplotypes/genetics
Female
Chemokine CCL2/*genetics
Carcinoma, Hepatocellular/epidemiology/etiology/genetics/virology
Aged, 80 and over
Aged
Adult
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