ABCMdb

PMID: 22132962

Nakayama A, Matsuo H, Takada T, Ichida K, Nakamura T, Ikebuchi Y, Ito K, Hosoya T, Kanai Y, Suzuki H, Shinomiya N
ABCG2 is a high-capacity urate transporter and its genetic impairment increases serum uric acid levels in humans.
Nucleosides Nucleotides Nucleic Acids. 2011 Dec;30(12):1091-7., [PubMed]

Sentences

No. Mutations Sentence Comment

28 ABCG2 p.Gln141Lys For quantitative trait locus (QTL) analysis of SUA concentrations, genotyping of Q141K in 739 Japanese individuals was performed. Login to comment 34 ABCG2 p.Gln141Lys ABCG2 p.Val12Met ABCG2 p.Gln126* With the site-directed mutagenesis technique, we constructed mutants of ABCG2 (V12M, Q126X, and Q141K), which were used for urate transport analysis, on the expression vector for ABCG2. Login to comment 47 ABCG2 p.Gln141Lys ABCG2 p.Val12Met ABCG2 p.Ser441Asn ABCG2 p.Gln126* ABCG2 p.Gly268Arg We found the following six nonsynonymous mutations: V12M, Q126X, Q141K, G268R, S441N, and F506SfsX4, and the first three mutations are SNPs. Login to comment 48 ABCG2 p.Gln141Lys ABCG2 p.Val12Met ABCG2 p.Gln126* Maekawa et al.[7] reported that these SNPs are quite common in the Japanese population, and allele frequencies for them are 31.9% for Q141K, 19.2% for V12M, and 2.8% for Q126X, respectively. Login to comment 49 ABCG2 p.Gln141Lys ABCG2 p.Val12Met ABCG2 p.Gln126* Using Hardy-Weinberg equilibrium and these data on a Japanese population reported by Maekawa et al.,[7] the frequencies of Japanese individuals with these minor alleles were estimated to be 53.6% for Q141K, 34.7% for V12M, and 5.5% for Q126X, respectively. Login to comment 50 ABCG2 p.Gln141Lys ABCG2 p.Gln126* [8] To clarify how ABCG2 SNPs affect function, the urate transport capacity of these variants was examined in comparison with that of wild-type ABCG2. ATP-dependent transport of urate was reduced by approximately half (46.7%) in Q141K and was nearly eliminated in Q126X (Figure 2A). Login to comment 51 ABCG2 p.Gln141Lys Common Variant of ABCG2 Increases SUA Levels in Humans With the high-frequency dysfunctional variant Q141K, QTL analysis of SUA was performed in a random sample of 739 Japanese individuals. Login to comment 52 ABCG2 p.Gln141Lys The analysis revealed a significant increase in SUA as the number of minor alleles of Q141K increased (p = 6.60 × 10-5 ), and the corrected p value is 2.02 × 10-6 when adjusted for sex (Figure 2B). Login to comment 54 ABCG2 p.Gln141Lys Unlike SUA, Q141K had no significant association with other clinical characteristics such as age, body mass index, or sex. Login to comment 58 ABCG2 p.Gln141Lys Results are expressed as means ± S.D. (B) QTL analysis of ABCG2 Q141K and serum uric acid levels. Login to comment 59 ABCG2 p.Gln141Lys "C/C," "C/A," and "A/A" indicate wild-type subjects, heterozygous mutation carriers, and homozygous mutation carriers of Q141K, respectively. Login to comment 62 ABCG2 p.Gln141Lys We also demonstrated that Q141K, a dysfunctional variant of ABCG2, significantly affects human SUA levels. Login to comment