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

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Dig Dis Sci. 2009 Dec;54(12):2722-8. Epub 2009 Sep 12.

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.

Source

Department of Biochemistry and Molecular Biology, Hanyang University College of

Medicine, Seoul, South Korea.

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.

© Springer Science+Business Media, LLC 2009