Single Nucleotide Polymorphisms of Cytokine Genes are Associated with Fibrosis of the Intrahepatic Bile Duct Wall in Human Clonorchiasis

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-gamma (+874 T/A), IL-10 (-1,082 G/A, -819 C/T, -592 C/A), TNF-alpha (-308 G/A), and TGF-beta1 (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-gamma intermediate-producing genotype, +874AT (80.0%, P = 0.177), and in those with TNF-alpha low-producing genotype, -308GG (63.0%, P = 0.148). According to the combination of IFN-gamma and TNF-alpha genotypes, the risks for IHDD could be stratified into high (intermediate-producing IFN-gamma and low producing TNF-alpha), moderate, and low (low-producing IFN-gamma and high producing TNF-alpha) 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-gamma and TNF-alpha genes may contribute to the modulation of fibrosis in the intrahepatic bile duct wall in clonorchiasis patients.