ABCMdb

PMID: 22000646

Anzai N, Endou H
Urate transporters: an evolving field.
Semin Nephrol. 2011 Sep;31(5):400-9., [PubMed]

Sentences

No. Mutations Sentence Comment

122 ABCG2 p.Gln141Lys Breast Cancer Resistance Protein BCRP (ABCG2) Breast cancer resistance protein BCRP is an adenosine triphosphate-binding cassette (ABC) transporter (ABCG2) originally isolated from doxorubicin-resistant breast cancer cells and mediates the transport of various chemicals, natural compounds, and drugs including several anticancer drugs such as methotrexate, mitoxantrone, topotecan, imatinib, and gefitinib.52,53 Although overexpression of BCRP is related to anticancer drug resistance in cancer cells, its endogenous messenger RNA expression was highest in the placenta and was high in the liver and intestine. Although the human kidney is known to express many drug efflux pumps at the apical side of proximal tubules such as P-glycoprotein/MDR1 (ABCB1), MRP2 (ABCC2), and MRP4 (ABCC4),54 evidence for BCRP expression in the kidney is somewhat confusing: according to one report, a moderate level of BCRP protein expression was detected despite no messenger RNA expression in the human kidney.52 Because BCRP also has a high affinity to porphyrins, it is responsible for cellular homeostasis of porphyrins, photosensitivity, and photodynamic therapy.53 Moreover, ABCG2 SNPs have been indicated to be an important factor for patients` adverse drug responses: for example, the most extensively studied ABCG2 SNP Q141K, associated with lower protein expression level and impaired transport activity in vitro, is related to increased plasma levels of gefitinib, increased bioavailability of oral topotecan, and Figure 2. Login to comment 130 ABCG2 p.Gln141Lys The earlier- mentioned hypoactive Q141K protein is associated with hyperuricemia. Login to comment 131 ABCG2 p.Gln141Lys BCRP recently was reported by Woodward et al18 to transport urate and they suggested that BCRP (ABCG2) is involved in urate excretion in the luminal membrane of renal proximal tubules. However, given its expression pattern (ie, high in the liver and intestine) and pathophysiological role of Q141K polymorphism in pharmacokinetics, it is likely that the hypoactive variant of ABCG2 leads to decreased urate excretion into the intestine rather than decreased urate excretion from the kidney. Login to comment