ABSTRACT
OBJECTIVE: Connective tissue growth factor (CTGF) has been proposed to play a key role in the pathogenesis of hepatic fibrosis in biliary atresia (BA). The aim of the present study was to determine the single nucleotide polymorphism (SNP) in the promoter region of CTGF gene in a Thai population, and to investigate the possible role of CTGF promoter polymorphism in the susceptibility of BA. MATERIAL AND METHOD: Genomic DNA was obtained from 84 patients with BA and 142 healthy controls. The -447 G/C and -132 C/G in CTGF promoter were amplified and examined by amplification-refractory mutation system (ARMs) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, respectively. The test of Hardy-Weinberg equilibrium (HWE) was performed using HWE program of SNPAnalyzer. Statistical analysis was carried out with SPSS and Epi Info. RESULT: According to the previous experiment, there were two SNPs, which were at position -447 and -132 on the promoter. However, there was only one SNP at the position -447 in the Thai population. No significant differences in genotype and allele frequency were observed between BA and controls or with BA subgroups. CONCLUSION: The present study demonstrated that CTGF polymorphism at -447 G/C was not associated with BA and the jaundice status of the postoperative BA patients.
Subject(s)
Alleles , Biliary Atresia/genetics , Case-Control Studies , Child , Connective Tissue , Connective Tissue Growth Factor , Disease Susceptibility , Female , Genotype , Humans , Immediate-Early Proteins/genetics , Intercellular Signaling Peptides and Proteins/genetics , Male , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Risk Factors , ThailandABSTRACT
Biliary atresia is a progressive obliterative cholangiopathy, but the etiology of this disorder remains uncertain. Identifying genes specifically expressed in biliary atresia and analyzing the pattern of expression may lead to a better understanding of the pathogenesis. Liver tissues were taken from a recipient with biliary atresia and a normal donor during liver transplantation. Total RNA was extracted from each sample and reversely transcribed to cDNA. Then radiolabeled cDNA probe pools were made by random primed DNA labeling method and used for screening of differentially expressed genes by hybridizing with expressed sequence tags (EST) dot blot panel. Northern blot hybridization was done to confirm that these genes are also differentially expressed in other liver tissues. Among 1,730 EST clones, 26 cDNA clones were significantly overexpressed in biliary cirrhosis, while 2 clones were significantly decreased in biliary atresia. By Northern blot hybridization, the results of tissue inhibitor of metalloproteinase (TIMP)-1 and IGFBP-2 were well correlated with differential EST screening (DES). This study identified the pattern of differentially expressed genes in the biliary cirrhosis due to biliary atresia using DES technique.
Subject(s)
Humans , Biliary Atresia/genetics , Blotting, Northern , Gene Expression Profiling/methods , Gene Library , Insulin-Like Growth Factor Binding Protein 2/genetics , Tissue Inhibitor of Metalloproteinase-1/geneticsABSTRACT
Extrahepatic biliary atresia (EHBA) is an infantile obstructive cholangiopathy of unknown etiology. This condition is generally thought to be an acquired disease without familial tendency. We reported eight pairs of discordant twins in a series of 143 patients with operatively established EHBA, One pair was dizygotic twin from sex discrimination. Six were identical ABO blood groups and 2 were also the same minor blood groups (Dce, MM and Le a-b-). The last 2 sets were monzygotic twins by common DNA polymorphisms short tandem repeat loci. Our findings support the hypothesis that, EHBA is an acquired rather than a hereditary disease.
Subject(s)
Alleles , Autoradiography , Biliary Atresia/genetics , Diseases in Twins/genetics , Female , Genotype , Humans , Male , Pedigree , Polymerase Chain Reaction , Repetitive Sequences, Nucleic Acid , Retrospective Studies , Twins/geneticsABSTRACT
Four pairs of discordant twins were observed in a series of 237 extrahepatic biliary atresia patients ascertained in London. The twinning prevalence (1.7%) was as expedcted considering the ethnic composition of the sample. Out of a total of 17 other twin pairs reported in the literature only one was concordant for the disease. Since only 17 instances of familial cases have been described, the conclusion is that any influence of genetic factors in this condition is likely to be manifested indirectly, possibly in the form of increased susceptibility of the biliary epithelium to infectious or toxic agents