title: Promoter polymorphism of the CD14 endotoxin receptor gene is associated with biliary atresia and idiopathic neonatal cholestasis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Chang-Gung Memorial Hospital at Chiayi, Pu-Tz City, Chiayi Hsien, Taiwan.
authors.forename: Hsiang-Hung
authors.initials: HH
authors.lastname: Shih
authors.forename: Tsun-Mei
authors.initials: TM
authors.lastname: Lin
authors.forename: Jiin-Haur
authors.initials: JH
authors.lastname: Chuang
authors.forename: Hock-Liew
authors.initials: HL
authors.lastname: Eng
authors.forename: Suh-Hang Hank
authors.initials: SH
authors.lastname: Juo
authors.forename: Fu-Chen
authors.initials: FC
authors.lastname: Huang
authors.forename: Chao-Long
authors.initials: CL
authors.lastname: Chen
authors.forename: Huey-Ling
authors.initials: HL
authors.lastname: Chen
mesh_terms: D000328:Adult; D001656:Biliary Atresia / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000601:surgery; D002648:Child; D002779:Cholestasis / Q000097:blood / Q000150:complications / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000235:genetics*; D008103:Liver Cirrhosis / Q000209:etiology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D018950:Lipopolysaccharide Receptors; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; C048071:endotoxin receptor