Breast Cancer Resistance Protein (BCRP)-Mediated Glyburide Transport: Effect of the C421A/Q141K BCRP Single-Nucleotide Polymorphism

Abstract

ABSTRACT:The antidiabetic agent glyburide (glibenclamide) is frequently used for the treatment of type II diabetes and is increasingly being used for the treatment of gestational diabetes. Evidence suggests that breast cancer resistance protein/ATP-binding cassette, subfamily

Genetic and Dietary Regulation of Glyburide Efflux by the Human Placental Breast Cancer Resistance Protein Transporter

“…2; Table 2). Whereas Pollex et al (2010) described BCRP protein cellsurface expression to be equal between genotypes, we observed less total (30%) and cell-surface (50%, P , 0.05) BCRP protein expression in the C421A-BCRP HEK cells (Fig. 1).…”

“…Others, however, have proposed that genistein can noncompetitively inhibit BCRP transport via disruption of ATP hydrolysis as well (Randak et al, 1999; Di Pietro et al, Genistein Reduces Placental BCRP Function and Expression 2002). To assess the mechanism of genistein inhibition, we used the 3 H-glyburide accumulation assay (Pollex et al, 2010) and Michaelis-Menten nonlinear regression analysis to calculate kinetic parameters (K m and J max ), which represent substrate affinity and rate of accumulation, respectively. It should be noted that because the assay measured Table 2).…”

“…Multiple transporters in the placenta interact with glyburide (Gedeon et al, 2006(Gedeon et al, , 2008a(Gedeon et al, , 2008bHemauer et al, 2010), significant evidence points to the breast cancer resistance protein (BCRP/ABCG2) as the major transporter responsible for the active extrusion of glyburide from the placenta. This has been demonstrated using BCRP-overexpressing cells, Bcrp knockout mice, pregnant rats, human placentas, and human placental vesicles (Pollex et al, 2008(Pollex et al, , 2010Zhou et al, 2008;Feinshtein et al, 2013).…”

“…A) in the ABCG2 gene leads to an amino acid change from glutamine to lysine (Q141K). In vitro, the C421A genotype is associated with reduced BCRP function (Kondo et al, 2004;Pollex et al, 2010). Importantly, the C421A genotype occurs frequently in Asian (C/A: 30%, A/A: 10%) and Caucasian (C/A: 15%, A/A: 1%) populations (Imai et al, 2002;Zamber et al, 2003;Kobayashi et al, 2005).…”

Determination of the Single Nucleotide Polymorphisms C3435 and G2677T in MDR1 and C421A in BCRP in Blood Samples of Patients with Inflammatory Bowel Disease and Healthy Controls in the Swiss Population

“…Clinical trials with diflomotecan, a novel anticancer agent inhibiting topoisomerase I, showed decreased plasma concentration in patients heterozygous for this SNP compared to wild type [33,34]. Recently, the increased placental crossing of the antidiabetic agent glyburide (glibenclamide) has been demonstrated in stably transfected human embryonic kidney (HEK)-293 cells expressing the polymorphic ABCG2 (Q141K) [35].…”