ABCMdb

PMID: 22473008

Ichida K, Matsuo H, Takada T, Nakayama A, Murakami K, Shimizu T, Yamanashi Y, Kasuga H, Nakashima H, Nakamura T, Takada Y, Kawamura Y, Inoue H, Okada C, Utsumi Y, Ikebuchi Y, Ito K, Nakamura M, Shinohara Y, Hosoyamada M, Sakurai Y, Shinomiya N, Hosoya T, Suzuki H
Decreased extra-renal urate excretion is a common cause of hyperuricemia.
Nat Commun. 2012 Apr 3;3:764. doi: 10.1038/ncomms1756., [PubMed]

Sentences

No. Mutations Sentence Comment

19 ABCG2 p.Gln141Lys Woodward et al. and our group independently found that ABCG2 transports urate and shows the reduced urate transport by a half-functional variant, Q141K (rs2231142)20,21. Login to comment 21 ABCG2 p.Gln141Lys ABCG2 p.Gln126* We also showed that common dysfunctional genotype combinations of ABCG2 gene (Q126X (rs72552713) and Q141K) are a major cause of gout21. Login to comment 28 ABCG2 p.Gln141Lys ABCG2 p.Gln126* The risk allele frequency of Q126X (risk allele, X) and Q141K (risk allele, K), among 644 male outpatients with hyperuricemia including 575 gout cases, was 4.1 and 45.9%, respectively. Login to comment 29 ABCG2 p.Gln141Lys ABCG2 p.Gln126* Those who had Q126X and Q141K variants were 8.1 and 71.9%, respectively, of all patients (Supplementary Table S2). Login to comment 30 ABCG2 p.Gln141Lys ABCG2 p.Gln126* Subsequent haplotype frequency analysis revealed that the minor alleles of Q126X and Q141K were in different haplotypes (Supplementary Table S3), which indicated that these variants were independent risks, as reported previously21. Login to comment 31 ABCG2 p.Gln141Lys ABCG2 p.Gln126* Therefore, we could estimate urate export function of ABCG2 by the combination of two common variants, non-functional Q126X and half-functional Q141K (Supplementary Fig. S1). Login to comment 82 ABCG2 p.Gln141Lys ABCG2 p.Gln141Lys ABCG2 p.Gln126* ABCG2 p.Gln126* Estimated transport activity Genotype N Frequency of OP hyperuricemia RR 95% CI P Adjusted RR† Adjusted 95% CI† Adjusted PȂ0; Q126X (rs72552713) Q141K (rs2231142) OP hyperuricemia* Non-OP hyperuricemia* ≤1/4 Function X/X Q/Q 26 3 0.897 2.35 1.86-2.97 3.32×10 - 7 2.30 1.31-3.90 2.65×10 - 3 Q/X Q/K 1/2 Function Q/X Q/Q 96 55 0.636 1.66 1.32-2.10 8.58×10 - 6 1.79 1.25-2.59 1.55×10 - 3 Q/Q K/K 3/4 Function Q/Q Q/K 160 147 0.521 1.36 1.09-1.71 4.55×10 - 3 1.42 1.03-2.00 0.035 Full function Q/Q Q/Q 60 97 0.382 1.00 Abbreviations: CI, confidence interval; OP, overproduction; RR, risk ratio. Login to comment 143 ABCG2 p.Gln141Lys ABCG2 p.Gln126* The export function of ABCG2 was then estimated from the combinations of ABCG2 variants, rs72552713 (Q126X) and rs2231142 (Q141K), and divided into four functional groups21; that is, full function, 3/4 function (mild dysfunction), 1/2 function (moderate dysfunction) and ≤1/4 function (severe dysfunction). Login to comment 146 ABCG2 p.Gln141Lys ABCG2 p.Gln126* The wild-type human ABCG2 cDNA (GenBank accession number NM_004827) or mutated (Q126X and Q141K) ABCG2 cDNA was inserted into the Nhe I and Apa I sites of pcDNA3.1( + ) vector plasmid, with a myc-tag sequence attached at the 5'-end21. Login to comment