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粪卟啉的尿排泄取决于ABCC2基因多态性，是人类多药耐药相关蛋白2（MRP2）活性的潜在生物标志物。

Urinary elimination of coproporphyrins is dependent on ABCC2 polymorphisms and represents a potential biomarker of MRP2 activity in humans.

作者信息

Benz-de Bretagne Isabelle, Respaud Renaud, Vourc'h Patrick, Halimi Jean-Michel, Caille Agnès, Hulot Jean-Sébastien, Andres Christian R, Le Guellec Chantal

机构信息

CHRU de Tours, Laboratoire de Biochimie et Biologie Moléculaire, Tours, France.

出版信息

J Biomed Biotechnol. 2011;2011:498757. doi: 10.1155/2011/498757. Epub 2011 Mar 14.

DOI:10.1155/2011/498757
PMID:21541183
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3085472/
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.

摘要

由ABCC2基因编码的多药耐药相关蛋白2（MRP2）参与多种药物和内源性底物的分泌。因ABCC2基因突变导致的杜宾-约翰逊综合征患者尿中粪卟啉比率（UCP I/(I + III)）升高。在此，我们研究了该比率是否可作为MRP2功能的生物标志物。通过测量74名健康受试者24小时尿液中的个体UCP I/(I + III)比率，并分析ABCC2基因中的五个常见单核苷酸多态性（SNP），研究了表型-基因型关系。在我们的研究人群中，UCP I/(I + III)比率在14.7%至46.0%之间变化。3972TT基因型的受试者比携带C等位基因的受试者具有更高的比率（P = .04）。这种较高的UCP I/(I + III)比率与异构体I排泄水平较高相关。本研究提供了一个概念验证，即UCP I/(I + III)比率可在临床研究中用作MRP2功能的生物标志物，因为它提供了关于特定患者体内MRP2活性的定量信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acf6/3085472/356d6bb4ac16/JBB2011-498757.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acf6/3085472/6e45cb1cef91/JBB2011-498757.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acf6/3085472/c9f886605a6e/JBB2011-498757.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acf6/3085472/0e8e8f3319e3/JBB2011-498757.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acf6/3085472/356d6bb4ac16/JBB2011-498757.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acf6/3085472/6e45cb1cef91/JBB2011-498757.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acf6/3085472/c9f886605a6e/JBB2011-498757.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acf6/3085472/0e8e8f3319e3/JBB2011-498757.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acf6/3085472/356d6bb4ac16/JBB2011-498757.004.jpg

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