A Proposal for Practical Diagnosis of Renal Hypouricemia: Evidenced from Genetic Studies of Nonfunctional Variants of URAT1/SLC22A12 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

doi:10.3390/biomedicines9081012

A Proposal for Practical Diagnosis of Renal Hypouricemia: Evidenced from Genetic Studies of Nonfunctional Variants of URAT1/SLC22A12 among 30,685 Japanese Individuals

Biomedicines. 2021 Aug 13;9(8):1012. doi: 10.3390/biomedicines9081012.

Authors

Yusuke Kawamura¹, Akiyoshi Nakayama¹, Seiko Shimizu¹, Yu Toyoda^{1

2}, Yuichiro Nishida³, Asahi Hishida⁴, Sakurako Katsuura-Kamano⁵, Kenichi Shibuya^{6

7}, Takashi Tamura⁴, Makoto Kawaguchi¹, Satoko Suzuki⁸, Satoko Iwasawa⁸, Hiroshi Nakashima⁸, Rie Ibusuki⁶, Hirokazu Uemura⁹, Megumi Hara³, Kenji Takeuchi⁴, Tappei Takada², Masashi Tsunoda⁸, Kokichi Arisawa⁵, Toshiro Takezaki⁶, Keitaro Tanaka³, Kimiyoshi Ichida^{10

11}, Kenji Wakai⁴, Nariyoshi Shinomiya¹, Hirotaka Matsuo¹

Affiliations

¹ Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan.
² Department of Pharmacy, Faculty of Medicine, The University of Tokyo Hospital, The University of Tokyo, Tokyo 113-8655, Japan.
³ Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan.
⁴ Department of Preventive Medicine, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan.
⁵ Department of Preventive Medicine, Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan.
⁶ Department of International Island and Community Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
⁷ Department of Emergency and Intensive Care Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
⁸ Department of Preventive Medicine and Public Health, National Defense Medical College, Tokorozawa 359-8513, Japan.
⁹ Department of Health and Welfare System, College of Nursing Art and Science, University of Hyogo, Akashi 673-8588, Japan.
¹⁰ Department of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan.
¹¹ Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo 105-8461, Japan.

Abstract

Background: Renal hypouricemia (RHUC) is characterized by a low serum uric acid (SUA) level and high fractional excretion of uric acid (FE_UA). Further studies on FE_UA 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 FE_UA data. The effects of NFV-URAT1 on FE_UA 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 FE_UA and decreased SUA, enabling FE_UA and SUA levels to be estimated. Conversely, FE_UA 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 FE_UA 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.

Keywords: URAT1/SLC22A12; fractional excretion of uric acid (FEUA); renal hypouricemia (RHUC); serum uric acid (SUA).

Abstract

Grants and funding