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A functional SNP of the interleukin-18 gene is associated with the presence of hepatocellular carcinoma in hepatitis B virus-infected patients.

Kim, YS; Cheong, JY; Cho, SW; Lee, KM; Hwang, JC; Oh, B; Kimm, K; Lee, JA; Park, BL; Cheong, HS; Shin, HD; Kim, JH
Digestive diseases and sciences, 54(12):2722-2728, 2009
Journal Title
Digestive diseases and sciences
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.
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Journal Papers > School of Medicine / Graduate School of Medicine > Gastroenterology
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