ABCMdb

PMID: 23166586

Kasza I, Varady G, Andrikovics H, Koszarska M, Tordai A, Scheffer GL, Nemeth A, Szakacs G, Sarkadi B
Expression levels of the ABCG2 multidrug transporter in human erythrocytes correspond to pharmacologically relevant genetic variations.
PLoS One. 2012;7(11):e48423. doi: 10.1371/journal.pone.0048423. Epub 2012 Nov 15., [PubMed]

Sentences

No. Mutations Sentence Comment

1 ABCG2 p.Gln141Lys Our method reveals significant differences between the expression levels of the wild-type ABCG2 protein and the heterozygous Q141K polymorphic variant. Login to comment 27 ABCG2 p.Gln141Lys Recently, a significant disease-association for a polymorphic ABCG2 variant (resulting in ABCG2-Q141K) has been observed in gout [24,25,26,27,28]. Login to comment 29 ABCG2 p.Gln141Lys A common variant of ABCG2 (c.421C.A; Q141K), with a variable allele frequency between 5-30% in various ethnic groups (see ref. [29]), was shown to decrease membrane protein expression in model PLOS ONE | www.plosone.org 1 November 2012 | Volume 7 | Issue 11 | e48423 Hungarian Academy of Sciences ( ) cells, despite unchanged mRNA levels [30,31,32,33,34]. Login to comment 30 ABCG2 p.Gln141Lys Still, a lower expression level of the ABCG2-Q141K variant has not been confirmed at physiologically relevant sites, given the difficulties in obtaining and processing human tissues. Login to comment 34 ABCG2 p.Gln141Lys In this report we show that individuals heterozygous for the potentially miss-processed ABCG2 variant (Q141K) have significantly lower ABCG2 protein expression in their red cells than individuals carrying the wild-type ABCG2 gene. Login to comment 67 ABCG2 p.Gln141Lys ABCG2 p.Val12Met The most common SNPs in ABCG2 [V12M (c.34G.A, p.12Val.Met in exon 2, SNP database ID: rs2231137) and Q141K (c.421C.A, p.141Gln.Lys in exon 5, SNP database ID: rs2231142] were genotyped using the LightCycler480 (Roche Diagnostics, Basle, Switzerland) allelic discrimination system as described previously in detail [45]. Login to comment 89 ABCG2 p.Gln141Lys ABCG2 p.Val12Met For this purpose we quantified the expression of the erythrocyte ABCG2 in 47 unrelated, healthy individuals that were also screened for the presence of two most prevalent ABCG2 polymorphic variants found in the Caucasian population (V12M and Q141K) [29]. Login to comment 101 ABCG2 p.Gln141Lys However, when the samples were grouped according to their genotypes, we found that the red blood cells of individuals carrying the heterozygous Q141K variant exhibited significantly lower expression of ABCG2 (5.2761.19), as compared to homozygous wild-type individuals (6.1360.61, p = 0.011) (Fig. 3). Login to comment 102 ABCG2 p.Val12Met There was no significant difference between homozygous wild-type individuals and heterozygous V12M carriers, although the number of the carriers of this variant was relatively low. Login to comment 103 ABCG2 p.Gln141Lys ABCG2 p.Val12Met As a summary of the ABCG2 polymorphism analysis data, among the 47 donors we found 11 individuals with the heterozygous presence of the DNA sequence coding for the Q141K variant (carrier frequency: 23.4%, allele frequency: 11.766.6%), and 3 individuals with the heterozygous presence of the V12M variant (carrier frequency: 6.4%; allele frequency: 3.263.6%). Login to comment 107 ABCG2 p.Arg236* A nonsense mutation, causing an arginine to stop codon change at codon 236 in exon 7 (c.706C.T, p.R236X, rs140207606 described previously [39,40]) was found in heterozygous form in proband 1. Login to comment 136 ABCG2 p.Gln141Lys ABCG2 p.Val12Met Labels: individuals carrying wild-type ABCG2 (WT), polymorphic (Q141K, V12M) ABCG2 alleles, or a heterozygous stop mutation (STOP). Login to comment 185 ABCG2 p.Gln141Lys Imai Y, Nakane M, Kage K, Tsukahara S, Ishikawa E, et al. (2002) C421A polymorphism in the human breast cancer resistance protein gene is associated with low expression of Q141K protein and low-level drug resistance. Login to comment 209 ABCG2 p.Gln141Lys Furukawa T, Wakabayashi K, Tamura A, Nakagawa H, Morishima Y, et al. (2009) Major SNP (Q141K) variant of human ABC transporter ABCG2 undergoes lysosomal and proteasomal degradations. Login to comment