PMID- 19757044 OWN - NLM STAT- MEDLINE DCOM- 20110421 LR - 20211020 IS - 1573-2568 (Electronic) IS - 0163-2116 (Linking) VI - 54 IP - 12 DP - 2009 Dec TI - A functional SNP of the Interleukin-18 gene is associated with the presence of hepatocellular carcinoma in hepatitis B virus-infected patients. PG - 2722-8 LID - 10.1007/s10620-009-0970-6 [doi] AB - BACKGROUND/AIM: 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. CI - (c) Springer Science+Business Media, LLC 2009 FAU - Kim, Yong Seok AU - Kim YS AD - Department of Biochemistry and Molecular Biology, Hanyang University College of Medicine, Seoul, South Korea. FAU - Cheong, Jae Youn AU - Cheong JY FAU - Cho, Sung Won AU - Cho SW FAU - Lee, Kee Myung AU - Lee KM FAU - Hwang, Jae Chul AU - Hwang JC FAU - Oh, Bermseok AU - Oh B FAU - Kimm, Kuchan AU - Kimm K FAU - Lee, Jung A AU - Lee JA FAU - Park, Byung Lae AU - Park BL FAU - Cheong, Hyun Sub AU - Cheong HS FAU - Shin, Hyoung Doo AU - Shin HD FAU - Kim, Jin Hong AU - Kim JH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090912 PL - United States TA - Dig Dis Sci JT - Digestive diseases and sciences JID - 7902782 RN - 0 (Interleukin-18) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Hepatocellular/*genetics/immunology/virology MH - Female MH - Gene Frequency MH - Genes, Reporter MH - Genetic Predisposition to Disease MH - Haplotypes MH - Hep G2 Cells MH - Hepatitis B, Chronic/*genetics/immunology MH - Humans MH - Interleukin-18/*genetics/metabolism MH - Linkage Disequilibrium MH - Liver Cirrhosis/genetics/immunology/virology MH - Liver Neoplasms/*genetics/immunology/virology MH - Logistic Models MH - Male MH - Middle Aged MH - Odds Ratio MH - Phenotype MH - *Polymorphism, Single Nucleotide MH - Promoter Regions, Genetic MH - Prospective Studies MH - Republic of Korea MH - Risk Assessment MH - Risk Factors MH - Transfection EDAT- 2009/09/17 06:00 MHDA- 2011/04/22 06:00 CRDT- 2009/09/17 06:00 PHST- 2009/06/17 00:00 [received] PHST- 2009/08/24 00:00 [accepted] PHST- 2009/09/17 06:00 [entrez] PHST- 2009/09/17 06:00 [pubmed] PHST- 2011/04/22 06:00 [medline] AID - 10.1007/s10620-009-0970-6 [doi] PST - ppublish SO - Dig Dis Sci. 2009 Dec;54(12):2722-8. doi: 10.1007/s10620-009-0970-6. Epub 2009 Sep 12.