ABCMdb

PMID: 20613716

Wright AF, Rudan I, Hastie ND, Campbell H
A 'complexity' of urate transporters.
Kidney Int. 2010 Sep;78(5):446-52. Epub 2010 Jul 7., [PubMed]

Sentences

No. Mutations Sentence Comment

35 ABCG2 p.Gln141Lys ABCG2 encodes an ATP binding cassette transporter, expressed in the apical membranes of several tissues, including liver and human proximal renal tubular cells, where it transports a wide variety of substrates, including urate.21 Recently, ABCG2 has been shown to encode a high-capacity urate secretion transporter.21,22 Several loss-of-function ABCG2 variants have also been identified that confer an increased risk of gout, including a common missense mutation (Q141K) within the nucleotide binding domain (next to the equivalent phenylalanine residue commonly mutated in cystic fibrosis), which was shown to reduce urate efflux in Xenopus oocytes by 53%.21 This variant appears to be the causal ABCG2 variant associated with raised serum urate and gout in GWAS meta-analyses.20,23 It confers an adjusted odds ratio of 1.68 per allele for gout and has a minor allele frequency of 3% in blacks, 11% in whites, and about 30% in Asians. Login to comment 36 ABCG2 p.Gln126* Other loss-of-function variants have been identified in the Japanese population (for example, Q126X in 5% of Japanese) so that variants at the ABCG2 locus have been estimated to account for about 10% of gout cases in both Caucasian and Japanese populations.21,22 The equivalent 'population attributable risk`-the proportional reduction in disease incidence if the associated variants could be removed from the population- for SLC2A9 is 55% of gout cases, because a very common SLC2A9 allele (frequency B77%) is associated with raised serum urate and the odds ratio for gout is similar to ABCG2, at 1.4 per allele.8 Population attributable risk figures are multiplicative, so that the combined reduction in gout due to these two loci would be 41% (0.9 Â 0.45). Login to comment