A Proposal for Practical Diagnosis of Renal Hypouricemia: Evidenced from Genetic Studies of Nonfunctional Variants of <i>URAT1/SLC22A12</i> among 30,685 Japanese Individuals
Yusuke Kawamura,
Akiyoshi Nakayama,
Seiko Shimizu,
Yu Toyoda,
Yuichiro Nishida,
Asahi Hishida,
Sakurako Katsuura-Kamano,
Kenichi Shibuya,
Takashi Tamura,
Makoto Kawaguchi,
Satoko Suzuki,
Satoko Iwasawa,
Hiroshi Nakashima,
Rie Ibusuki,
Hirokazu Uemura,
Megumi Hara,
Kenji Takeuchi,
Tappei Takada,
Masashi Tsunoda,
Kokichi Arisawa,
Toshiro Takezaki,
Keitaro Tanaka,
Kimiyoshi Ichida,
Kenji Wakai,
Nariyoshi Shinomiya,
Hirotaka Matsuo
Affiliations
Yusuke Kawamura
Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan
Akiyoshi Nakayama
Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan
Seiko Shimizu
Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan
Yu Toyoda
Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan
Yuichiro Nishida
Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan
Asahi Hishida
Department of Preventive Medicine, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan
Sakurako Katsuura-Kamano
Department of Preventive Medicine, Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan
Kenichi Shibuya
Department of International Island and Community Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan
Takashi Tamura
Department of Preventive Medicine, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan
Makoto Kawaguchi
Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan
Satoko Suzuki
Department of Preventive Medicine and Public Health, National Defense Medical College, Tokorozawa 359-8513, Japan
Satoko Iwasawa
Department of Preventive Medicine and Public Health, National Defense Medical College, Tokorozawa 359-8513, Japan
Hiroshi Nakashima
Department of Preventive Medicine and Public Health, National Defense Medical College, Tokorozawa 359-8513, Japan
Rie Ibusuki
Department of International Island and Community Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan
Hirokazu Uemura
Department of Health and Welfare System, College of Nursing Art and Science, University of Hyogo, Akashi 673-8588, Japan
Megumi Hara
Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan
Kenji Takeuchi
Department of Preventive Medicine, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan
Tappei Takada
Department of Pharmacy, Faculty of Medicine, The University of Tokyo Hospital, The University of Tokyo, Tokyo 113-8655, Japan
Masashi Tsunoda
Department of Preventive Medicine and Public Health, National Defense Medical College, Tokorozawa 359-8513, Japan
Kokichi Arisawa
Department of Preventive Medicine, Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan
Toshiro Takezaki
Department of International Island and Community Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan
Keitaro Tanaka
Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan
Kimiyoshi Ichida
Department of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan
Kenji Wakai
Department of Preventive Medicine, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan
Nariyoshi Shinomiya
Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan
Hirotaka Matsuo
Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan
Background: Renal hypouricemia (RHUC) is characterized by a low serum uric acid (SUA) level and high fractional excretion of uric acid (FEUA). Further studies on FEUA in hypouricemic individuals are needed for a more accurate diagnosis of RHUC. Methods: In 30,685 Japanese health-examination participants, we genotyped the two most common nonfunctional variants of URAT1 (NFV-URAT1), W258X (rs121907892) and R90H (rs121907896), in 1040 hypouricemic individuals (SUA ≤ 3.0 mg/dL) and 2240 individuals with FEUA data. The effects of NFV-URAT1 on FEUA and SUA were also investigated using linear and multiple regression analyses. Results: Frequency of hypouricemic individuals (SUA ≤ 3.0 mg/dL) was 0.97% (male) and 6.94% (female) among 30,685 participants. High frequencies of those having at least one allele of NFV-URAT1 were observed in 1040 hypouricemic individuals. Furthermore, NFV-URAT1 significantly increased FEUA and decreased SUA, enabling FEUA and SUA levels to be estimated. Conversely, FEUA and SUA data of hypouricemic individuals are revealed to be useful to predict the number of NFV-URAT1. Conclusions: Our findings reveal that specific patterns of FEUA and SUA data assist with predicting the number of nonfunctional variants of causative genes for RHUC, and can also be useful for practical diagnosis of RHUC even before genetic tests.
