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Research on the Relationship between Bile Salt Export Pump Gene Polymorphism and Cholestasis in Idiopathic Infantile Hepatitis

Author: DengYaZuo
Tutor: WangLinLin
School: Guangxi Medical University
Course: Pediatrics
Keywords: BSEP Baby Intrahepatic cholestasis Single nucleotide polymorphism analysis Restriction fragment length polymorphism
CLC: R725.7
Type: Master's thesis
Year: 2011
Downloads: 18
Quote: 0
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Abstract


BACKGROUND AND OBJECTIVE: Idiopathic infantile hepatitis intrahepatic cholestasis pathogenesis is not clear, bile salt export pump (BSEP) mainly in the bile capillary surface of liver cells by ATP-dependent bile within the liver cells secreted into Bile, the bile flow is affecting one of the most important factors, the present study indicates that BSEP gene with a variety of cholestatic liver diseases. In this study, idiopathic infantile hepatitis intrahepatic cholestasis often found in children with BSEP gene mutations in exons were screened to explore whether the bile salt export pump gene with idiopathic infantile hepatitis intrahepatic cholestasis related. Methods: 2008-10 to 2010-02, First Affiliated Hospital of Guangxi Medical University hospital idiopathic infantile hepatitis intrahepatic cholestasis in children 81 cases as case group and 48 patients without cholestasis babies as the control group, the application Polymerase chain reaction - single strand conformation polymorphism (PCR-SSCP) method BSEP exon 2,3,4,5,6,9,10,13,16,17,23,24 for testing. Abnormal bands for exons were sequenced, the results on the gene pool in Genbank sequence comparison, using polymerase chain - restriction fragment length polymorphism (PCR-RFLP) technique SNPs were genotyped . Results: In the BSEP exon 13 was detected on a single nucleotide polymorphism loci V444A, case and control groups AA, AG and GG genotype frequencies were 4.9%, 50.6%, 44.4% and 14.6 %, 62.5%, 22.9% respectively, there was significant difference (P = 0.019); with GG genotype had idiopathic infantile hepatitis intrahepatic cholestasis increased risk, OR value of 2.691 (95% CI: 1.205-6.008); G allele carriers suffering from idiopathic infantile hepatitis risk of intrahepatic cholestasis of 1.951 times the A allele (OR = 1.951,95% CI: 1.56-3.291). In the BSEP exon 24 SNP loci detected on the A1028A, encoded amino acid unchanged, are alanine (Ala), BSEP A1028A genotype and allele frequencies between cases and control group had no significant difference in the distribution , still can not believe BSEP A1028A idiopathic infantile hepatitis intrahepatic cholestasis of a risk factor. Other exon 10 mutations were not found exception. Conclusion: 1, BSEP V444A single-stranded nucleotide polymorphism may be associated with infant intrahepatic cholestasis, BSEP V444A G allele may be idiopathic infantile hepatitis intrahepatic cholestasis of a risk factor, G allele carriers may increase idiopathic infantile hepatitis intrahepatic cholestasis prevalence risk; 2, BSEP A1028A with idiopathic infantile hepatitis intrahepatic cholestasis occurs susceptibility. 3, BSEP gene exon 2,3,4,5,6,9,10,16,17,23 found no suspicious mutations.

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