Mutation analysis of the multidrug resistance protein 2 (MRP2) gene in a Japanese patient with Dubin?Johnson syndrome

Role of Multidrug Resistance Associated Proteins in Drug Development

“…The absence of functional MRP2 is the molecular basis of transport defect of DJS (283). Many single nucleotide polymorphisms in DJS patients have been reported (Table 2) (118,(284)(285)(286)(287)(288). These include C-24T (promoter), G1249A (exon 10), G2026C (exon 16), T2125C (exon 17), C2302T (exon 18), C2366 (exon 18), A3517T (exon 25), G3449 (exon 25), C3972T (exon 28) and G4348A (Exon 31) ( Table 2).…”

Bilirubin Metabolism and its Disorders

“…[177][178][179] More than a dozen genetic lesions, including nucleotide transition of a single nucleotide deletion, resulting in amino acid substitutions, premature truncation, or exon skipping, have been reported to cause Dubin-Johnson syndrome. 385 Some of the reported mutations may lead to impaired glycosylation of the MRP2 protein, impaired sorting to the canalicular membrane, and premature proteasomedependent degradation. 386 As in TR -rats and EHBR rats, the absence of MRP2 (mrp2 in rats) in the canalicular membrane causes severe impairment of canalicular secretion of bilirubin conjugates, the leukotriene LTC 4 , reduced and oxidized glutathione, and numerous glucuronide and glutathione-conjugates.…”

Multidrug resistance proteins (MRPs) and implication in drug development

“…The absence of functional MRP2 is the molecular basis of transport defect of DJS . Many single nucleotide polymorphisms in DJS patients have been reported (Table 2) Mor-Cohen et al, 2001;Suzuki and Sugiyama, 2002;Wakusawa et al, 2003;Hirouchi et al, 2004;Machida et al, 2004]. These include C-24T (promoter), G1249A (exon 10), G2026C (exon 16), T2125C (exon 17), C2302T (exon 18), C2366 (exon 18), A3517T (exon 25), G3449 (exon 25), C3972T (exon 28) and G4348A (Exon 31) ( Table 2).…”

“…A total of 51 10q23-24 C-24T Promoter Suzuki and Sugiyama, 2002] Val417Ile G1249A Exon10 Suzuki and Sugiyama, 2002;Hirouchi et al, 2004] Gly676Arg G2026C Exon16 [Wakusawa et al, 2003] Try709Arg T2125C Exon17 [Machida et al, 2004] Arg768Trp C2302T Exon18 Suzuki and Sugiyama, 2002;Hirouchi et al, 2004 mutations were identified and 15 SNPs were located in the coding exons of MRP3, six of which are nonsynonymous mutations. The SNPs G39GC (allele frequency=0.5%, in exon 1), C202T (1.6%, exon 2), C1037T (0.5%, exon 9), C1537A (0.5%, exon 12), G3890A (5.2%, exon 27), and G4267A (0.6%, exon 29) led to Lys13Asn, His68Tyr, Ser346Phe, Gln513Lys, Arg1297His, and Gly1423Arg amino acid substitutions, respectively (Table 2).…”