Published in:
01-12-2009 | Original Article
A Functional SNP of the Interleukin-18 Gene Is Associated with the Presence of Hepatocellular Carcinoma in Hepatitis B Virus-Infected Patients
Authors:
Yong Seok Kim, Jae Youn Cheong, Sung Won Cho, Kee Myung Lee, Jae Chul Hwang, Bermseok Oh, Kuchan Kimm, Jung A. Lee, Byung Lae Park, Hyun Sub Cheong, Hyoung Doo Shin, Jin Hong Kim
Published in:
Digestive Diseases and Sciences
|
Issue 12/2009
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Abstract
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.