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. 2009 Nov 4;1(5):5ra11.
doi: 10.1126/scitranslmed.3000237.

Common defects of ABCG2, a high-capacity urate exporter, cause gout: a function-based genetic analysis in a Japanese population

Hirotaka Matsuo  1 , Tappei Takada, Kimiyoshi Ichida, Takahiro Nakamura, Akiyoshi Nakayama, Yuki Ikebuchi, Kousei Ito, Yasuyoshi Kusanagi, Toshinori Chiba, Shin Tadokoro, Yuzo Takada, Yuji Oikawa, Hiroki Inoue, Koji Suzuki, Rieko Okada, Junichiro Nishiyama, Hideharu Domoto, Satoru Watanabe, Masanori Fujita, Yuji Morimoto, Mariko Naito, Kazuko Nishio, Asahi Hishida, Kenji Wakai, Yatami Asai, Kazuki Niwa, Keiko Kamakura, Shigeaki Nonoyama, Yutaka Sakurai, Tatsuo Hosoya, Yoshikatsu Kanai, Hiroshi Suzuki, Nobuyuki Hamajima, Nariyoshi Shinomiya
Affiliations

Common defects of ABCG2, a high-capacity urate exporter, cause gout: a function-based genetic analysis in a Japanese population

Hirotaka Matsuo et al. Sci Transl Med. .

Abstract

Gout based on hyperuricemia is a common disease with a genetic predisposition, which causes acute arthritis. The ABCG2/BCRP gene, located in a gout-susceptibility locus on chromosome 4q, has been identified by recent genome-wide association studies of serum uric acid concentrations and gout. Urate transport assays demonstrated that ABCG2 is a high-capacity urate secretion transporter. Sequencing of the ABCG2 gene in 90 hyperuricemia patients revealed several nonfunctional ABCG2 mutations, including Q126X. Quantitative trait locus analysis of 739 individuals showed that a common dysfunctional variant of ABCG2, Q141K, increases serum uric acid. Q126X is assigned to the different disease haplotype from Q141K and increases gout risk, conferring an odds ratio of 5.97. Furthermore, 10% of gout patients (16 out of 159 cases) had genotype combinations resulting in more than 75% reduction of ABCG2 function (odds ratio, 25.8). Our findings indicate that nonfunctional variants of ABCG2 essentially block gut and renal urate excretion and cause gout.

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