Research On The Relationship Between Bile Salt Export Pump Gene Polymorphism And Cholestasis In Idiopathic Infantile Hepatitis

Background and Purpose: The aetiology of cholestasis in idiopathic infantile hepatitis was unclear yet. It is found that BSEP is mainly located in the bile capillary surface of liver cells, bile of the liver cells will be secreted into the bile capillaries through depend on ATP, and it is one of the most important factors about bile flow. Recently the study indicate that BSEP gene go with a variety of cholestatic liver disease. This study intend to screen several common variations on the bile salt export pump (BSEP) gene and to evaluate genetic factors in the pathogenesis of cholestasis in idiopathic infantile hepatitis.Methods: Firstly, enrolling 81 cases of cholestasis in idiopathic infantile hepatitis as the case group and 48 patients without cholestasis as the control group, those who are hospitalized on the department of Pediatrics of the First Affliated Hospital of Guangxi Medical University from Oct.2008. to Feb.2010. Genomic DNA was extracted from peripheral venous blood leukocytes of research objects. The polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SSCP) were used to inspect the BSEP gene exon 2,3,4,5,6,9,10,13,16,17,23,24. The PCR products were used by single strand conformation polymorphism (SSCP), and the abnormal bands of exons were sequenced. Comparing the result of sequence with the gene pool of Genbank and then combining with polymerase chain reaction - restriction fragment length polymorphism (PCR -RFLP) technology to genotype polymorphisms in order to research genotyped.Results: BSEP gene exon 13 is discovered in the single nucleotide polymorphism V444A, AA , AG and GG 3 genotypes in case group and control group frequency, it account for 50.6%, 4.9%, 44.4% and 14.6%, 62.5%, 22.9% respectively,the difference was significant (P = 0.019). Allele frequencies of the relative risk analysis showed that GG genotype in which the distribution of the difference in the two groups was noticeable (P <0.05, OR = 2.691, 95% CI: 1.205-6.008); G allele carriers suffering from idiopathic intrahepatic cholestasis in infants risk of hepatitis A allele was 1.951 times (OR = 1.951, 95% CI: 1.56-3.291). The exon 24 was detected on BSEP A1028A synonymous mutations, amino acid does not change,and both are alanine (Ala). BSEP A1028A genotype and allele frequencies in cases and healthy control group make no significant differences in the distribution. All the same, it can not believe that BSEP A1028A associated idiopathic intrahepatic cholestasis in infants of hepatitis were not a risk factors. The other 10 exons were not found exception mutation.Conclusions:1. BSEP V444A single-stranded nucleotide polymorphism may be associated with idiopathic intrahepatic cholestasis in infants. ABCB11 V444A G allele may be a risk factor about idiopathic intrahepatic cholestasis in infants of hepatitis, and G allele carriers may increase infant hepatitis idiopathic cholestasis of relative risk. 2.These data suggest that BSEP A1028A synonymous mutations are not associated with susceptibility to the pathogenesis of idiopathic infant cholestasis. 3.Suspicious mutation was not found in BSEP gene exon 2,3,4,5,6,9,10,16,17,23.