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Single Nucleotide Polymorphisms of Cytokine Genes are Associated with Fibrosis of the Intrahepatic Bile Duct Wall in Human Clonorchiasis
Authors:Byung-Suk Chung  Jeong-Keun Lee  Min-Ho Choi  Myoung Hee Park  Dongil Choi  and Sung-Tae Hong
Institution:1Department of Parasitology and Tropical Medicine and Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul 110-799, Korea.;2Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul 110-799, Korea.;3Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea.
Abstract:This study examined the association of cytokine gene polymorphisms with intrahepatic bile duct wall fibrosis in human clonorchiasis. A total of 240 residents in Heilongjiang, China underwent ultrasonography, blood sampling, and stool examination. Single nucleotide polymorphism (SNP) sites for IFN-γ (+874 T/A), IL-10 (-1,082 G/A, -819 C/T, -592 C/A), TNF-α (-308 G/A), and TGF-β1 (codon 10 T/C, codon 25 G/C) genes were observed with the TaqMan allelic discrimination assay. No significant correlation was observed between individual cytokine gene polymorphisms and intrahepatic duct dilatation (IHDD). Among individuals with clonorchiasis of moderate intensity, the incidence of IHDD was high in those with IFN-γ intermediate-producing genotype, +874AT (80.0%, P = 0.177), and in those with TNF-α low-producing genotype, -308GG (63.0%, P = 0.148). According to the combination of IFN-γ and TNF-α genotypes, the risks for IHDD could be stratified into high (intermediate-producing IFN-γ and low producing TNF-α), moderate, and low (low-producing IFN-γ and high producing TNF-α) risk groups. The incidence of IHDD was significantly different among these groups (P = 0.022): 88.9% (odds ratio, OR = 24.0) in high, 56.5% (OR = 3.9) in moderate, and 25.0% (OR = 1) in low risk groups. SNP of IFN-γ and TNF-α genes may contribute to the modulation of fibrosis in the intrahepatic bile duct wall in clonorchiasis patients.
Keywords:Clonorchis sinensis  IFN-γ  IL-10  TNF-α  TGF-β1  single nucleotide polymorphism  bile duct  fibrosis
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