The study demonstrates that C allele of rs916145 in USF2 gene has more frequency for developing BA, and decreased USF2 protein nuclear translocation might partly play a role in the decreased hepcidin expression in the cholestatic liver injury of the late stage of BA.
Increased expression of genes encoding Notch ligand JAG1 and its receptor NOTCH2 was observed in BA livers compared with control by quantitative polymerase chain reaction analyses.
We analysed 30 subjects with Alagille syndrome, nine with incomplete Alagille syndrome and 17 with biliary atresia and detected pathogenic mutations in JAG1 or NOTCH2 in 24/30 subjects with Alagille syndrome and in 4/9 subjects with incomplete Alagille syndrome.
Comparisons between the Jagged and Delta family show a huge diversity in the structures of the loops at the apex of the C2 domain implicated in membrane recognition and Jagged1 missense mutations, which affect these loops and are associated with extrahepatic biliary atresia, lead to a loss of membrane recognition, but do not alter Notch binding.
We examined the JAG1 mutation in extrahepatic biliary atresia (EHBA), which is similar in phenotype to AGS, although a different pathogenesis is suggested.
As a member of membrane skeletal proteins in the liver and bile ducts, a haplotype composed by five single nucleotide polymorphisms (SNPs) on adducin 3 (<i>ADD3</i>) has been identified as associated with BA.
Hepatic mRNA levels of interferon-gamma or interleukin-4 showed no significant differences between BA and non-BA, while FoxP3 was significantly higher in BA (<i>p</i> = 0.01).
This study suggests that the ADD3 gene plays an important role in BA pathogenesis and reveals a significant association between two SNPs, rs17095355 and rs10509906, and BA.
Moreover, in bioinformatics and in vivo genotype-expression investigations, the BA-associated potentially regulatory SNPs correlated with ADD3 gene expression (n=36; p=0.0030).
IFN-γ mRNA expression levels in BA patients were also significantly increased, and the IFN-γ gene promoter region was hypomethylated in BA CD4+ T cells compared with controls and negatively correlated with DNA methylation.
In the first, we interrogated the hepatic transcriptome of children with biliary atresia and found an interferon-gamma (IFNgamma)-rich proinflammatory footprint at the time of diagnosis.
The median serum MMP-7 levels were 38.89 ng/mL (interquartile range: 22.96-56.46) for the BA group and 4.4 ng/mL (interquartile range: 2.73-6.56) for the non-BA group (<i>P</i> < .001).