title: A functional SNP of the Interleukin-18 gene is associated with the presence of hepatocellular carcinoma in hepatitis B virus-infected patients.
abstract: OBJECTIVE
  The natural course of hepatitis B virus (HBV) infection is likely related to host immune factors. Interleukin-18 (IL-18) plays a significant role in immune defense. This study was undertaken to determine the association between the presence of hepatocellular carcinoma (HCC) and single-nucleotide polymorphisms (SNPs) in the IL-18 gene in HBV-infected patients.
  
  
  METHODS
  Between March 2002 and December 2004, 730 Korean subjects were enrolled in two different groups: (1) chronic carrier without HCC (n=637) and (2) HCC (n=93). We analyzed SNPs at four polymorphic sites in the IL-18 gene at positions -667G>T, -148G>C, +8925C>G, and +13925A>C in the study subjects. To evaluate the functional significance of SNPs in the IL-18 gene promoter region, we performed a reporter gene assay in HepG2 and Hep3B cells transfected with different alleles.
  
  
  RESULTS
  The IL-18 -148C allele, +8925G allele, +13925C allele, and haplotype 3 (TCGC) were associated with the presence of HCC in codominant and dominant models. Furthermore, functional analyses using the reporter gene assay revealed that the -148C allele conferred significantly lower promoter activity.
  
  
  CONCLUSIONS
  This study indicates that the -148C, +8925G, and +13925C alleles of the IL-18 gene are associated with the presence of HCC and the 148G>C SNP is functionally important in determining disease outcome.
authors.affiliation: Department of Biochemistry and Molecular Biology, Hanyang University College of Medicine, Seoul, South Korea.
authors.forename: Yong Seok
authors.initials: YS
authors.lastname: Kim
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Cheong
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Cho
authors.forename: Kee Myung
authors.initials: KM
authors.lastname: Lee
authors.forename: Jae Chul
authors.initials: JC
authors.lastname: Hwang
authors.forename: Bermseok
authors.initials: B
authors.lastname: Oh
authors.forename: Kuchan
authors.initials: K
authors.lastname: Kimm
authors.forename: Jung A
authors.initials: JA
authors.lastname: Lee
authors.forename: Byung Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: Jin Hong
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000276:immunology / Q000821:virology; D005260:Female; D005787:Gene Frequency; D017930:Genes, Reporter; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D056945:Hep G2 Cells; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000276:immunology; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics* / Q000378:metabolism; D015810:Linkage Disequilibrium; D008103:Liver Cirrhosis / Q000235:genetics / Q000276:immunology / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics* / Q000276:immunology / Q000821:virology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D056910:Republic of Korea; D018570:Risk Assessment; D012307:Risk Factors; D014162:Transfection
chemical_list: D020382:Interleukin-18