Association of IL18 genetic polymorphisms with increased risk of Biliary atresia susceptibility in Southern Chinese children

Biliary atresia (BA) has complex genetic etiology, characterized by different levels of hepatic fibrosis after the Kasai procedure and immune responses to the bile duct. As an activator of the two most important inflammatory cells in Biliary atresia (T cells and NK cells), IL-18 is significantly increased in BA patients. This study aims to investigate the association of Interleukin 18(IL-18) with the susceptibility to BA. We examined the association of three polymorphisms (rs549908, rs187238 and rs1946518 in IL-18) and BA susceptibility in a Southern Chinese population composed of 506 cases and 1473 controls. SNP rs187238 and rs1946518 were identified as associated with BA. Interestingly, we also observed that the intragenic synergistic epistasis between SNPs rs187238 and rs1946518 boosting the risk to BA by logistic regression and Multifactor dimensionality reduction (MDR) analysis. This study provides for the first time a direct evidence to support IL-18 as a susceptibility gene for the disease in southern Chinese children.