ABCG2 dysfunction causes hyperuricemia due to both renal urate underexcretion and renal urate overload.
Gout is a common disease which results from hyperuricemia. We have reported that the dysfunction of urate exporter ABCG2 is the major cause of renal overload (ROL) hyperuricemia, but its involvement in renal underexcretion (RUE) hyperuricemia, the most prevalent subtype, is not clearly explained so far. In this study, the association analysis with 644 hyperuricemia patients and 1,623 controls in male Japanese revealed that ABCG2 dysfunction significantly increased the risk of RUE hyperuricemia as well as overall and ROL hyperuricemia, according to the severity of impairment. ABCG2 dysfunction caused renal urate underexcretion and induced hyperuricemia even if the renal urate overload was not remarkable. These results show that ABCG2 plays physiologically important roles in both renal and extra-renal urate excretion mechanisms. Our findings indicate the importance of ABCG2 as a promising therapeutic and screening target of hyperuricemia and gout.
1] Department of Integrative Physiology and Bio-Nano Medicine National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan [2].
Hirotaka
H
Matsuo
1] Department of Integrative Physiology and Bio-Nano Medicine National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan [2] Medical Group, Headquarters, Iwo-to Air Base Group, Japan Air Self-Defense Force, Iwo-to, Ogasawara, Tokyo 100-2100, Japan [3].
Akiyoshi
A
Nakayama
Department of Integrative Physiology and Bio-Nano Medicine National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
Masayuki
M
Sakiyama
Department of Integrative Physiology and Bio-Nano Medicine National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
Toshinori
T
Chiba
Department of Integrative Physiology and Bio-Nano Medicine National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
Seiko
S
Shimizu
Department of Integrative Physiology and Bio-Nano Medicine National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
Yusuke
Y
Kawamura
Department of Preventive Medicine and Public Health, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
Hiroshi
H
Nakashima
1] Laboratory for Mathematics, Premedical Course, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan [2] Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, RIKEN, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Takahiro
T
Nakamura
Laboratory for Biofunctions, The Central Research Institute, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
Yuzo
Y
Takada
Department of Biology, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
Yuji
Y
Oikawa
Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Tappei
T
Takada
Department of Integrated Genetics, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540, Japan.
Hirofumi
H
Nakaoka
Department of Integrative Physiology and Bio-Nano Medicine National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
Junko
J
Abe
Department of Integrative Physiology and Bio-Nano Medicine National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
Hiroki
H
Inoue
Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Kenji
K
Wakai
Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Sayo
S
Kawai
1] Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan [2] Department of Nutritional Sciences, Faculty of Health and Welfare, Seinan Jo Gakuin University, 1-3-5 Ibori, Kokura Kita-ku, Kitakyushu, Fukuoka 803-0835, Japan.
Yin
Y
Guang
Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Hiroko
H
Nakagawa
Department of Internal Medicine, Self-Defense Forces Central Hospital, 1-2-24 Ikejiri, Setagaya-ku, Tokyo 154-8532, Japan.
Toshimitsu
T
Ito
Department of Biology, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
Kazuki
K
Niwa
Division of Genome Analysis, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Ken
K
Yamamoto
Department of Preventive Medicine and Public Health, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
Yutaka
Y
Sakurai
Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Hiroshi
H
Suzuki
Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, 3-19-18 Shinbashi, Minato-ku, Tokyo 105-8471, Japan.
Tatsuo
T
Hosoya
1] Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, 3-19-18 Shinbashi, Minato-ku, Tokyo 105-8471, Japan [2] Department of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachiouji, Tokyo 192-0392, Japan.
Kimiyoshi
K
Ichida
Midorigaoka Hospital, 3-13-1 Makami-cho, Takatsuki, Osaka 569-1121, Japan.
Toru
T
Shimizu
Department of Integrative Physiology and Bio-Nano Medicine National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
Nariyoshi
N
Shinomiya
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000483:Alleles; D005838:Genotype; D006801:Humans; D033461:Hyperuricemia / Q000209:etiology*; D007674:Kidney Diseases / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D014527:Uric Acid / Q000378:metabolism* / Q000652:urine
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D014527:Uric Acid