TY - JOUR
T1 - A proposal for practical diagnosis of renal hypouricemia
T2 - Evidenced from genetic studies of nonfunctional variants of urat1/slc22a12 among 30,685 japanese individuals
AU - Kawamura, Yusuke
AU - Nakayama, Akiyoshi
AU - Shimizu, Seiko
AU - Toyoda, Yu
AU - Nishida, Yuichiro
AU - Hishida, Asahi
AU - Katsuura-Kamano, Sakurako
AU - Shibuya, Kenichi
AU - Tamura, Takashi
AU - Kawaguchi, Makoto
AU - Suzuki, Satoko
AU - Iwasawa, Satoko
AU - Nakashima, Hiroshi
AU - Ibusuki, Rie
AU - Uemura, Hirokazu
AU - Hara, Megumi
AU - Takeuchi, Kenji
AU - Takada, Tappei
AU - Tsunoda, Masashi
AU - Arisawa, Kokichi
AU - Takezaki, Toshiro
AU - Tanaka, Keitaro
AU - Ichida, Kimiyoshi
AU - Wakai, Kenji
AU - Shinomiya, Nariyoshi
AU - Matsuo, Hirotaka
N1 - Funding Information:
Funding: This study was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, including JSPS KAKENHI Grants (Nos. 20H00566, 20K23152, 20K10522, 21H03350, 17H04128, 25293145, 221S0002 and 16H06279), the Ministry of Defense, the Kawano Masanori Memorial Foundation for the Promotion of Pediatrics and the Gout Research Foundation of Japan. The J-MICC Study was supported by Grants-in-Aid for Scientific Research from MEXT, including those for Priority Areas (No. 17015018) and Innovative Areas (No. 221S0001), as well as by a JSPS KAKENHI grant (No. 16H06277 [CoBiA]).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/8
Y1 - 2021/8
N2 - 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 ob-served 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.
AB - 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 ob-served 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.
KW - Fractional excretion of uric acid (FE)
KW - Renal hypouricemia (RHUC)
KW - Serum uric acid (SUA)
KW - URAT1/SLC22A12
UR - http://www.scopus.com/inward/record.url?scp=85113312234&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85113312234&partnerID=8YFLogxK
U2 - 10.3390/biomedicines9081012
DO - 10.3390/biomedicines9081012
M3 - Article
AN - SCOPUS:85113312234
SN - 2227-9059
VL - 9
JO - Biomedicines
JF - Biomedicines
IS - 8
M1 - 1012
ER -