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

• Main Authors: 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
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: Biomedicines
• Subjects: <i>URAT1/SLC22A12</i>; renal hypouricemia (RHUC); serum uric acid (SUA); fractional excretion of uric acid (FE_UA)
• Online Access: https://www.mdpi.com/2227-9059/9/8/1012
• ISSN: 2227-9059

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 <i>URAT1</i> (NFV-<i>URAT1</i>), 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-<i>URAT1</i> 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-<i>URAT1</i> were observed in 1040 hypouricemic individuals. Furthermore, NFV-<i>URAT1</i> 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-<i>URAT1</i>. 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.