title: Hyperuricemia in acute gastroenteritis is caused by decreased urate excretion via ABCG2.
abstract: To clarify the physiological and pathophysiological roles of intestinal urate excretion via ABCG2 in humans, we genotyped ABCG2 dysfunctional common variants, Q126X (rs72552713) and Q141K (rs2231142), in end-stage renal disease (hemodialysis) and acute gastroenteritis patients, respectively. ABCG2 dysfunction markedly increased serum uric acid (SUA) levels in 106 hemodialysis patients (P = 1.1 × 10(-4)), which demonstrated the physiological role of ABCG2 for intestinal urate excretion because their urate excretion almost depends on intestinal excretion via ABCG2. Also, ABCG2 dysfunction significantly elevated SUA in 67 acute gastroenteritis patients (P = 6.3 × 10(-3)) regardless of the degree of dehydration, which demonstrated the pathophysiological role of ABCG2 in acute gastroenteritis. These findings for the first time show ABCG2-mediated intestinal urate excretion in humans, and indicates the physiological and pathophysiological importance of intestinal epithelium as an excretion pathway besides an absorption pathway. Furthermore, increased SUA could be a useful marker not only for dehydration but also epithelial impairment of intestine.
authors: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan.
authors: Hirotaka
authors: H
authors: Matsuo
authors: Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Kanagawa 230-0012, Japan.
authors: Tomoyuki
authors: T
authors: Tsunoda
authors: Ryougoku East Gate Clinic, Sumida-ku, Tokyo 130-0026, Japan.
authors: Keiko
authors: K
authors: Ooyama
authors: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan.|Department of Dermatology, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan.
authors: Masayuki
authors: M
authors: Sakiyama
authors: Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Kanagawa 230-0012, Japan.
authors: Tsuyoshi
authors: T
authors: Sogo
authors: Department of Pharmacy, The University of Tokyo Hospital, Bunkyo-ku, Tokyo 113-8655, Japan.
authors: Tappei
authors: T
authors: Takada
authors: Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Minato-ku, Tokyo 105-8471, Japan.
authors: Akio
authors: A
authors: Nakashima
authors: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan.
authors: Akiyoshi
authors: A
authors: Nakayama
authors: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan.|Department of Urology, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan.
authors: Makoto
authors: M
authors: Kawaguchi
authors: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan.
authors: Toshihide
authors: T
authors: Higashino
authors: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi 461-8673, Japan.
authors: Kenji
authors: K
authors: Wakai
authors: Ryougoku East Gate Clinic, Sumida-ku, Tokyo 130-0026, Japan.
authors: Hiroshi
authors: H
authors: Ooyama
authors: Department of Internal Medicine, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan.
authors: Ryota
authors: R
authors: Hokari
authors: Department of Pharmacy, The University of Tokyo Hospital, Bunkyo-ku, Tokyo 113-8655, Japan.
authors: Hiroshi
authors: H
authors: Suzuki
authors: Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Minato-ku, Tokyo 105-8471, Japan.|Department of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors: Kimiyoshi
authors: K
authors: Ichida
authors: Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Kanagawa 230-0012, Japan.
authors: Ayano
authors: A
authors: Inui
authors: Department of Internal Medicine, Teikyo University School of Medicine, Itabashi-ku, Tokyo 173-8605, Japan.
authors: Shin
authors: S
authors: Fujimori
authors: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan.
authors: Nariyoshi
authors: N
authors: Shinomiya
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000378:metabolism*; D005759:Gastroenteritis / Q000150:complications*; D006801:Humans; D033461:Hyperuricemia / Q000503:physiopathology*; D066237:Intestinal Elimination; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D044967:Serum / Q000737:chemistry; D014527:Uric Acid / Q000378:metabolism*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D009363:Neoplasm Proteins; D014527:Uric Acid