Sequence analysis of bile salt export pump (ABCB11) and multidrug resistance p-glycoprotein 3 (ABCB4, MDR3) in patients with intrahepatic cholestasis of pregnancy

摘要: Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder associated with increased risk intrauterine fetal death and prematurity. There increasing evidence that genetically determined dysfunction in the canalicular ABC transporters bile salt export pump (BSEP, ABCB11) multidrug resistance protein 3 (MDR3, ABCB4) might be factors for ICP development. This study aimed to (i). describe extent genetic variability BSEP MDR3 (ii). identify new disease-causing mutations. Twenty-one women 40 uneventful pregnancies were recruited between April 2001 2003. Sequencing spanned 8-10 kb per gene comprised promoter region 100-350 bp flanking intronic around each exon. DNA sequencing polymerase chain reaction fragments was performed on an ABI3700 capillary sequencer. activity constructs carrying different ICP-specific mutations studied using reporter assays. A total 37 51 variant sites detected MDR3, respectively. Three non-synonymous codons evolutionarily conserved amino acids specific collective N591S; S320F G762E). Furthermore, four splicing [intron 21, G(+1)A; intron 25, G(+5)C C(-3)G; 26, T(+2)A]. Activity mutated similar observed wild-type promoter. Our data further support involvement variation pathogenesis ICP, whereas analysis sequence indicates this probably less important development pregnancy-associated cholestasis.