title: Urinary elimination of coproporphyrins is dependent on ABCC2 polymorphisms and represents a potential biomarker of MRP2 activity in humans.
abstract: MRP2 encoded by ABCC2 gene is involved in the secretion of numerous drugs and endogenous substrates. Patients with Dubin-Johnson syndrome due to mutation in ABCC2 gene have elevated urinary coproporphyrin ratio (UCP I/(I + III)). Here we investigated whether this ratio could serve as a biomarker of MRP2 function. Phenotype-genotype relationships were studied in 74 healthy subjects by measuring individual UCP I/(I + III) ratio obtained on 24-hour urine and by analyzing five common SNPs in ABCC2 gene. The UCP I/(I + III) ratio varied from 14.7% to 46.0% in our population. Subjects with 3972TT genotype had a higher ratio (P = .04) than those carrying the C allele. This higher UCP I/(I + III) ratio was correlated with a higher level of isomer I excretion. This study provides a proof of concept that UCP I/(I + III) ratio can be used as a biomarker of MRP2 function in clinical studies as it provides quantitative information about the in vivo activity of MRP2 in a given patient.
authors.affiliation: CHRU de Tours, Laboratoire de Biochimie et Biologie Moléculaire, Tours, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Benz-de Bretagne
authors.forename: Renaud
authors.initials: R
authors.lastname: Respaud
authors.forename: Patrick
authors.initials: P
authors.lastname: Vourc'h
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Halimi
authors.forename: Agnès
authors.initials: A
authors.lastname: Caille
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Hulot
authors.forename: Christian R
authors.initials: CR
authors.lastname: Andres
authors.forename: Chantal
authors.initials: C
authors.lastname: Le Guellec
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D003306:Coproporphyrins / Q000652:urine*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006262:Health; D006801:Humans; D008297:Male; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D003306:Coproporphyrins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C000715087:ABCC2 protein, human