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.
© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.