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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Promoter polymorphism of the CD14 endotoxin receptor gene is associated with biliary atresia and idiopathic neonatal cholestasis.

OBJECTIVE: To investigate whether single-nucleotide polymorphisms in the promoter regions of endotoxin-responsive genes CD14 and tumor necrosis factor-alpha (TNF-alpha) 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-alpha/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-alpha/-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.[1]

References

  1. Promoter polymorphism of the CD14 endotoxin receptor gene is associated with biliary atresia and idiopathic neonatal cholestasis. Shih, H.H., Lin, T.M., Chuang, J.H., Eng, H.L., Juo, S.H., Huang, F.C., Chen, C.L., Chen, H.L. Pediatrics (2005) [Pubmed]
 
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