Objective.To investigate whether single-nucleotide polymorphisms in the promoter regions of endotoxin-responsive genes CD14 and tumor necrosis factor-α (TNF-α) are associated with biliary atresia (BA) and idiopathic neonatal cholestasis (INC).

Methods.We obtained genomic DNA from 90 patients with established diagnosis of BA and 28 patients with INC. Forty-two adult patients with hepatitis B–related cirrhosis and 143 healthy children served as control populations. The genotypes of CD14/C(−159)T and TNF-α/G(−308)A (G allele, TNF*1; A allele, TNF*2) were determined by using a restriction enzyme–based assay. Plasma soluble CD14 levels were determined in different disease stages and genotypes of BA.

Results.The frequencies of T allele and T/T homozygosity of the CD14/−159 promoter polymorphism were significantly higher in patients with BA (T allele: 61.7%; T/T genotype: 42.2%) and in patients with INC (T allele: 67.9%; T/T genotype: 53.6%) but not in control populations. Decrease of plasma soluble CD14 from the early stage of BA when the patients received a Kasai operation to the late stage of liver cirrhosis was observed in carriers of the T/T and T/C genotypes but not in carriers of the C/C genotype. The TNF-α/−308 promoter polymorphisms (TNF*1 and TNF*2) were not associated with BA.

Conclusion.These findings show that the single-nucleotide polymorphism at CD14/−159 is associated with the development of BA and INC. Endotoxin susceptibility may play a role in the pathogenesis of infantile cholestasis.

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