ABCMdb

PMID: 24909660

Nakayama A, Matsuo H, Nakaoka H, Nakamura T, Nakashima H, Takada Y, Oikawa Y, Takada T, Sakiyama M, Shimizu S, Kawamura Y, Chiba T, Abe J, Wakai K, Kawai S, Okada R, Tamura T, Shichijo Y, Akashi A, Suzuki H, Hosoya T, Sakurai Y, Ichida K, Shinomiya N
Common dysfunctional variants of ABCG2 have stronger impact on hyperuricemia progression than typical environmental risk factors.
Sci Rep. 2014 Jun 9;4:5227. doi: 10.1038/srep05227., [PubMed]

Sentences

No. Mutations Sentence Comment

18 ABCG2 p.Gln141Lys ABCG2 p.Gln126* Based on the previous studies8,11 , all of the participants were divided into four groups by the combination of common dysfunctional variants of ABCG2, non-functional Q126X (rs72552713) and half-functional Q141K (rs2231142), as follows: full function (normal function), 3/ 4 function (mild dysfunction), 1/2 function (moderate dysfunction) and #1/4 function (severe dysfunction) (see Supplementary Figure S1 and Table S2). Login to comment 36 ABCG2 p.Gln126* We also found that ABCG2 has two common dysfunctional variants: a nonsense variant Q126X and a missense variant Q141K8 . Login to comment 37 ABCG2 p.Gln141Lys ABCG2 p.Gln126* Functional analyses revealed that Q126X is a nonfunctional variant and Q141K is a half-functional variant due to the halved ABCG2 expression on the membrane8 . Login to comment 38 ABCG2 p.Gln141Lys ABCG2 p.Gln141Lys ABCG2 p.Gln126* ABCG2 p.Gln126* Since haplotype frequency analyses demonstrated no simultaneous presence of the minor alleles of Q126X and Q141K in one haplotype, the combination of nonfunctional variant Q126X and half-functional variant Q141K makes it possible to estimate dysfunctional levels of ABCG28,10 (Supplementary Figure S1 and Table S2). Login to comment 45 ABCG2 p.Gln141Lys As for the relationship between SNPs and the risk of hyperuricemia, Woodward et al. so far reported that the PAR% of Q141K for gout was 10% in Caucasians7 , and Yamagishi et al. indicated that PAR% for gout and/or hyperuricemia was 19% in Japanese16 . Login to comment 46 ABCG2 p.Gln141Lys ABCG2 p.Gln126* Ours is the first report to show the PAR% of ABCG2 dysfunction using the combination of Q126X and Q141K for functional evaluation. Login to comment 47 ABCG2 p.Gln141Lys It is reasonable that the PAR% of Q141K in Caucasians would be lower than that in Japanese, because the minor allele frequency in Caucasians (0.11 according to Woodward et al.7 ) is lower than those of Japanese (0.31 by Yamagishi et al.16 and 0.29 in the present study). Login to comment 48 ABCG2 p.Gln141Lys When we re-calculated PAR% according to the definition of hyperuricemia in Yamagishi et al.16 (SUA $ 7.0 mg/dl), the resulting PAR% of Q141K was 22.2%, which is comparable to that in Yamagishi et al.16 . Login to comment 49 ABCG2 p.Gln141Lys ABCG2 p.Gln126* In the present study, we defined hyperuricemia as SUA .7.0 mg/dl17 and obtained the PAR% of Q141K and Q126X as 23.5% and 2.6%, respectively. Login to comment 52 ABCG2 p.Gln141Lys ABCG2 p.Gln126* Subsequent regression analysis revealed that ABCG2 dysfunction defined by the combination of Q126X and Q141K significantly increased SUA, while previous studies showed the association of SUA and only Q141K7,8 . Login to comment 76 ABCG2 p.Gln141Lys ABCG2 p.Gln126* Genotyping of the two variants in ABCG2 gene, Q126X and Q141K, was performed with a LightCycler 480 (Roche Diagnostics) by high resolution melting (HRM) analysis22 . Login to comment 79 ABCG2 p.Gln141Lys ABCG2 p.Gln126* The MAFs of Q126X and Q141K were 0.025 and 0.294, respectively, and both variants were in Hardy-Weinberg equilibrium (P . Login to comment