Urinary Elimination of Coproporphyrins Is Dependent onABCC2 Polymorphisms and Represents a Potential Biomarker of MRP2 Activity in Humans

• Published in: BioMed research international Vol. 2011; no. 2011; pp. 1 - 9
• Main Authors: Le Guellec, Chantal, Hulot, Jean-Sébastien, Caille, Agnès, Halimi, Jean-Michel, Vourc'h, Patrick, Respaud, Renaud, Benz-de Bretagne, Isabelle, Andres, Christian
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2011; Hindawi Limited
• Subjects: Biomarkers; Biomedical research; Mutation; Rodents
• ISSN: 2314-6133; 1110-7243; 2314-6141; 1110-7251
• DOI: 10.1155/2011/498757

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.