A Preliminary Study Of FXR, MDR3 Gene On The Pathogenesis Of Cholestasis In Idiopathic Infantile Hepatitis

Background and Aim: The aetiology of cholestasis in idiopathic infantile hepatitis was unclear yet. It knows that farnesoid X receptor (FXR) is a bile acid-activated nuclear receptor that played a major role in bile acid metabolism. The multidrug resistance protein 3(MDR3) is a member of the ABC superfamily transport carrier, MDR3 protein was mainly distributed in the liver, bile capillary membrane. As a phospholipid transport carrier, it played an important role in phospholipids and bile secretion. This study aimed to sceen the FXR and MDR3 gene variations and to evaluate genetic factors in the pathogenesis of cholestasis in idiopathic infantile hepatitis.Methods: A case–control study was performed which enrolled 78 idiopathic infant hepatitis with cholestasis patients who hospitalized on the First Affiliated Hospital of Guangxi Medical University from 2008-3 to 2009-5 and enrolled 40 infants without cholestasis in control group. Genomic DNA was extracted from peripheral venous blood leukocytes using phenol chloroform methodology. The polymerase chain reaction(PCR) and single-strand conformation polymorphism(SSCP) were used to detect the mutations on FXR gen and MDR3 exon4, 6, 8,12,14,16. The PCR products which had abnormal bands in SSCP were sequenced by DNA sequencer.Results: A heterozygous nonsense mutation in FXR exon 5 R176X (CGA > TGA) was found in one case among the 78 patients. But the other patients and controls were all negative for polymorphisms;A MDR3 single nucleotide polymorphisms(SNP) was found in exon 16 (R652G), The R652G allele was significant more frequent in healthy infant(8.0%) than in patient control (2.60%), P < 0.05, odds ratio, 0.29; 95% confidence interval (CI), 0.12-0.84. The conjugated bilirubin of AG genotype (44.70±6.15μmol/L) was significantly lower compared with AA genotype (95.52±5.93μmol/L) in patients MDR3 R652G gene type sub-group analysis, P < 0.05.Conclusions: This study found a novel heterozygous nonsense mutation in FXR R176X. A novel mutation adds further information on the involvement of the FXR gene in intrahepatic cholestasis that may be useful in differential diagnosis of idiopathic infant cholestasis and to establish the influence of such gene defect in the prognosis; MDR3 R652G has a high frequency of normal infants in the Guangxi region. And R652G children may reduce susceptibility suffering from cholestasis of idiopathic infant hepatitis in Guangxi of China.