The association of immune-related genes and the potential role of IL10 with biliary atresia

Background Biliary atresia (BA) is a severe immune-related disease that is characterized by biliary obstruction and cholestasis. The etiology of BA is unclear, our aim was to explore the relationship between biliary tract inflammation and immune-related genes. Methods We selected 14 SNPs in 13 immune-related genes and investigated their associations with BA by using a large case‒control cohort with a total of 503 cases and 1473 controls from southern China. Results SNP rs1518111 in interleukin10 ( IL10 ) was identified as associated with BA ( P = 5.79E-03; OR: 0.80; 95% CI: 0.68–0.94). The epistatic effects of the following pairwise interactions among these SNPs were associated with BA: signal transducer and activator of transcription 4 ( STAT4 ) and chemokine (C-X-C motif) ligand 3 ( CXCL3 ); STAT4 and damage-regulated autophagy modulator1 ( DRAM1 ); CXCL3 and RAD51 paralog B ( RAD51B ); and interferon gamma ( IFNG ) and interleukin26 ( IL26 ). Furthermore, we explored the potential role of IL-10 in the pathogenesis of the neonatal mouse model of BA. IL-10 effectively prevented biliary epithelial cell injury and biliary obstruction in murine BA as well as inhibit the activation of BA-related immune cells. Conclusions In conclusion, this study provided strong evidence implicating IL10 as a susceptibility gene for BA in the southern Chinese population. Impact This study provided strong evidence implicating IL10 as a susceptibility gene for BA in the southern Chinese population. This study could infer that IL-10 may play a protective role in BA mouse model. We found that four SNPs (rs7574865, rs352038, rs4622329, and rs4902562) have genetic interactions.