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

Hirotaka Matsuo, 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 MorimotoMariko 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

研究成果: Article

215 引用 (Scopus)

抄録

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.

元の言語English
記事番号5ra11
ジャーナルScience Translational Medicine
1
発行部数5
DOI
出版物ステータスPublished - 04-11-2009

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Gout
Uric Acid
Population
Hyperuricemia
Odds Ratio
Quantitative Trait Loci
Genome-Wide Association Study
Genetic Predisposition to Disease
Serum
Haplotypes
Genes
Arthritis
Chromosomes
Genotype
Mutation

All Science Journal Classification (ASJC) codes

  • Medicine(all)

これを引用

Matsuo, Hirotaka ; Takada, Tappei ; Ichida, Kimiyoshi ; Nakamura, Takahiro ; Nakayama, Akiyoshi ; Ikebuchi, Yuki ; Ito, Kousei ; Kusanagi, Yasuyoshi ; Chiba, Toshinori ; Tadokoro, Shin ; Takada, Yuzo ; Oikawa, Yuji ; Inoue, Hiroki ; Suzuki, Koji ; Okada, Rieko ; Nishiyama, Junichiro ; Domoto, Hideharu ; Watanabe, Satoru ; Fujita, Masanori ; Morimoto, Yuji ; Naito, Mariko ; Nishio, Kazuko ; Hishida, Asahi ; Wakai, Kenji ; Asai, Yatami ; Niwa, Kazuki ; Kamakura, Keiko ; Nonoyama, Shigeaki ; Sakurai, Yutaka ; Hosoya, Tatsuo ; Kanai, Yoshikatsu ; Suzuki, Hiroshi ; Hamajima, Nobuyuki ; Shinomiya, Nariyoshi. / Common defects of ABCG2, a high-capacity urate exporter, cause gout : A function-based genetic analysis in a Japanese population. :: Science Translational Medicine. 2009 ; 巻 1, 番号 5.
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title = "Common defects of ABCG2, a high-capacity urate exporter, cause gout: A function-based genetic analysis in a Japanese population",
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.",
author = "Hirotaka Matsuo and Tappei Takada and Kimiyoshi Ichida and Takahiro Nakamura and Akiyoshi Nakayama and Yuki Ikebuchi and Kousei Ito and Yasuyoshi Kusanagi and Toshinori Chiba and Shin Tadokoro and Yuzo Takada and Yuji Oikawa and Hiroki Inoue and Koji Suzuki and Rieko Okada and Junichiro Nishiyama and Hideharu Domoto and Satoru Watanabe and Masanori Fujita and Yuji Morimoto and Mariko Naito and Kazuko Nishio and Asahi Hishida and Kenji Wakai and Yatami Asai and Kazuki Niwa and Keiko Kamakura and Shigeaki Nonoyama and Yutaka Sakurai and Tatsuo Hosoya and Yoshikatsu Kanai and Hiroshi Suzuki and Nobuyuki Hamajima and Nariyoshi Shinomiya",
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Matsuo, H, Takada, T, Ichida, K, Nakamura, T, Nakayama, A, Ikebuchi, Y, Ito, K, Kusanagi, Y, Chiba, T, Tadokoro, S, Takada, Y, Oikawa, Y, Inoue, H, Suzuki, K, Okada, R, Nishiyama, J, Domoto, H, Watanabe, S, Fujita, M, Morimoto, Y, Naito, M, Nishio, K, Hishida, A, Wakai, K, Asai, Y, Niwa, K, Kamakura, K, Nonoyama, S, Sakurai, Y, Hosoya, T, Kanai, Y, Suzuki, H, Hamajima, N & Shinomiya, N 2009, 'Common defects of ABCG2, a high-capacity urate exporter, cause gout: A function-based genetic analysis in a Japanese population', Science Translational Medicine, 巻. 1, 番号 5, 5ra11. https://doi.org/10.1126/scitranslmed.3000237

Common defects of ABCG2, a high-capacity urate exporter, cause gout : A function-based genetic analysis in a Japanese population. / Matsuo, Hirotaka; Takada, Tappei; Ichida, Kimiyoshi; Nakamura, Takahiro; Nakayama, Akiyoshi; Ikebuchi, Yuki; Ito, Kousei; Kusanagi, Yasuyoshi; Chiba, Toshinori; Tadokoro, Shin; Takada, Yuzo; Oikawa, Yuji; Inoue, Hiroki; Suzuki, Koji; Okada, Rieko; Nishiyama, Junichiro; Domoto, Hideharu; Watanabe, Satoru; Fujita, Masanori; Morimoto, Yuji; Naito, Mariko; Nishio, Kazuko; Hishida, Asahi; Wakai, Kenji; Asai, Yatami; Niwa, Kazuki; Kamakura, Keiko; Nonoyama, Shigeaki; Sakurai, Yutaka; Hosoya, Tatsuo; Kanai, Yoshikatsu; Suzuki, Hiroshi; Hamajima, Nobuyuki; Shinomiya, Nariyoshi.

:: Science Translational Medicine, 巻 1, 番号 5, 5ra11, 04.11.2009.

研究成果: Article

TY - JOUR

T1 - Common defects of ABCG2, a high-capacity urate exporter, cause gout

T2 - A function-based genetic analysis in a Japanese population

AU - Matsuo, Hirotaka

AU - Takada, Tappei

AU - Ichida, Kimiyoshi

AU - Nakamura, Takahiro

AU - Nakayama, Akiyoshi

AU - Ikebuchi, Yuki

AU - Ito, Kousei

AU - Kusanagi, Yasuyoshi

AU - Chiba, Toshinori

AU - Tadokoro, Shin

AU - Takada, Yuzo

AU - Oikawa, Yuji

AU - Inoue, Hiroki

AU - Suzuki, Koji

AU - Okada, Rieko

AU - Nishiyama, Junichiro

AU - Domoto, Hideharu

AU - Watanabe, Satoru

AU - Fujita, Masanori

AU - Morimoto, Yuji

AU - Naito, Mariko

AU - Nishio, Kazuko

AU - Hishida, Asahi

AU - Wakai, Kenji

AU - Asai, Yatami

AU - Niwa, Kazuki

AU - Kamakura, Keiko

AU - Nonoyama, Shigeaki

AU - Sakurai, Yutaka

AU - Hosoya, Tatsuo

AU - Kanai, Yoshikatsu

AU - Suzuki, Hiroshi

AU - Hamajima, Nobuyuki

AU - Shinomiya, Nariyoshi

PY - 2009/11/4

Y1 - 2009/11/4

N2 - 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.

AB - 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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U2 - 10.1126/scitranslmed.3000237

DO - 10.1126/scitranslmed.3000237

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