Urinary Elimination of Coproporphyrins Is Dependent on ABCC2 Polymorphisms and Represents a Potential Biomarker of MRP2 Activity in Humans

الملخص EN

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.