Shih H.-H.Lin T.-M.Chuang J.-H.Eng H.-L.Suh-Hang H.J.Huang F.-C.Chen C.-L.HUEY-LING CHEN2020-03-102020-03-1020050031-4005https://www.scopus.com/inward/record.uri?eid=2-s2.0-33644613510&doi=10.1542%2fpeds.2004-1900&partnerID=40&md5=40f6927551ba880f18828f3a2e8573d5https://scholars.lib.ntu.edu.tw/handle/123456789/475177Objective. 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. Copyright ? 2005 by the American Academy of Pediatrics.EnglishBiliary atresia; CD14 gene; Endotoxin susceptibility; Neonatal cholestasis; Single nucleotide polymorphism[SDGs]SDG3CD14 antigen; genomic DNA; tumor necrosis factor alpha; endotoxin receptor; immunoglobulin receptor; allele; article; bile duct atresia; cholestasis; controlled study; DNA polymorphism; female; genetic analysis; genotype; human; liver cirrhosis; major clinical study; male; newborn disease; portoenterostomy; priority journal; single nucleotide polymorphism; adult; bile duct atresia; blood; child; cholestasis; gene frequency; genetics; homozygote; liver cirrhosis; newborn; promoter region; single nucleotide polymorphism; Adult; Antigens, CD14; Biliary Atresia; Child; Cholestasis; Female; Gene Frequency; Genotype; Homozygote; Humans; Infant, Newborn; Liver Cirrhosis; Male; Polymorphism, Single Nucleotide; Promoter Regions (Genetics); Receptors, Immunologic; Tumor Necrosis Factor-alphajournal article10.1542/peds.2004-1900160616002-s2.0-33644613510