Association of common promoter polymorphisms of MCP1 with hepatitis B virus clearance.
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.
Park
Byung Lae
BL
Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul 153-803, Korea.
Kim
Yoon Jun
YJ
Cheong
Hyun Sub
HS
Kim
Lyoung Hyo
LH
Choi
Yoo Hyun
YH
Lee
Hyo-Suk
HS
Shin
Hyoung Doo
HD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000209:etiology / Q000235:genetics / Q000821:virology; D018932:Chemokine CCL2 / Q000235:genetics*; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006509:Hepatitis B / Q000150:complications / Q000235:genetics* / Q000628:therapy / Q000821:virology*; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*
D018932:Chemokine CCL2