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

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

Background: Renal hypouricemia (RHUC) is characterized by a low serum uric acid (SUA) level and high fractional excretion of uric acid (FE<sub>UA</sub>). Further studies on FE<sub>UA</sub> in hypouricemic individuals are needed for a more accurate diagnosis of RHUC. Methods:...

Full description

Bibliographic Details
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<sub>UA</sub>)
Online Access:https://www.mdpi.com/2227-9059/9/8/1012
id doaj-374df1a21f18430bb1805654d36a9794
record_format Article
collection DOAJ
language English
format Article
sources DOAJ
author 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
spellingShingle 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
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
Biomedicines
<i>URAT1/SLC22A12</i>
renal hypouricemia (RHUC)
serum uric acid (SUA)
fractional excretion of uric acid (FE<sub>UA</sub>)
author_facet 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
author_sort Yusuke Kawamura
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort proposal for practical diagnosis of renal hypouricemia: evidenced from genetic studies of nonfunctional variants of <i>urat1/slc22a12</i> among 30,685 japanese individuals
publisher MDPI AG
series Biomedicines
issn 2227-9059
publishDate 2021-08-01
description Background: Renal hypouricemia (RHUC) is characterized by a low serum uric acid (SUA) level and high fractional excretion of uric acid (FE<sub>UA</sub>). Further studies on FE<sub>UA</sub> 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<sub>UA</sub> data. The effects of NFV-<i>URAT1</i> on FE<sub>UA</sub> 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<sub>UA</sub> and decreased SUA, enabling FE<sub>UA</sub> and SUA levels to be estimated. Conversely, FE<sub>UA</sub> 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<sub>UA</sub> 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.
topic <i>URAT1/SLC22A12</i>
renal hypouricemia (RHUC)
serum uric acid (SUA)
fractional excretion of uric acid (FE<sub>UA</sub>)
url https://www.mdpi.com/2227-9059/9/8/1012
work_keys_str_mv AT yusukekawamura aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT akiyoshinakayama aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT seikoshimizu aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT yutoyoda aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT yuichironishida aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT asahihishida aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT sakurakokatsuurakamano aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT kenichishibuya aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT takashitamura aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT makotokawaguchi aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT satokosuzuki aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT satokoiwasawa aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT hiroshinakashima aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT rieibusuki aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT hirokazuuemura aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT megumihara aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT kenjitakeuchi aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT tappeitakada aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT masashitsunoda aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT kokichiarisawa aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT toshirotakezaki aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT keitarotanaka aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT kimiyoshiichida aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT kenjiwakai aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT nariyoshishinomiya aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT hirotakamatsuo aproposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT yusukekawamura proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT akiyoshinakayama proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT seikoshimizu proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT yutoyoda proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT yuichironishida proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT asahihishida proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT sakurakokatsuurakamano proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT kenichishibuya proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT takashitamura proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT makotokawaguchi proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT satokosuzuki proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT satokoiwasawa proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT hiroshinakashima proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT rieibusuki proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT hirokazuuemura proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT megumihara proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT kenjitakeuchi proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT tappeitakada proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT masashitsunoda proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT kokichiarisawa proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT toshirotakezaki proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT keitarotanaka proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT kimiyoshiichida proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT kenjiwakai proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT nariyoshishinomiya proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
AT hirotakamatsuo proposalforpracticaldiagnosisofrenalhypouricemiaevidencedfromgeneticstudiesofnonfunctionalvariantsofiurat1slc22a12iamong30685japaneseindividuals
_version_ 1721194685850976256
spelling doaj-374df1a21f18430bb1805654d36a97942021-08-26T13:33:09ZengMDPI AGBiomedicines2227-90592021-08-0191012101210.3390/biomedicines9081012A Proposal for Practical Diagnosis of Renal Hypouricemia: Evidenced from Genetic Studies of Nonfunctional Variants of <i>URAT1/SLC22A12</i> among 30,685 Japanese IndividualsYusuke Kawamura0Akiyoshi Nakayama1Seiko Shimizu2Yu Toyoda3Yuichiro Nishida4Asahi Hishida5Sakurako Katsuura-Kamano6Kenichi Shibuya7Takashi Tamura8Makoto Kawaguchi9Satoko Suzuki10Satoko Iwasawa11Hiroshi Nakashima12Rie Ibusuki13Hirokazu Uemura14Megumi Hara15Kenji Takeuchi16Tappei Takada17Masashi Tsunoda18Kokichi Arisawa19Toshiro Takezaki20Keitaro Tanaka21Kimiyoshi Ichida22Kenji Wakai23Nariyoshi Shinomiya24Hirotaka Matsuo25Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, JapanDepartment of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, JapanDepartment of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, JapanDepartment of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, JapanDepartment of Preventive Medicine, Faculty of Medicine, Saga University, Saga 849-8501, JapanDepartment of Preventive Medicine, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, JapanDepartment of Preventive Medicine, Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8503, JapanDepartment of International Island and Community Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, JapanDepartment of Preventive Medicine, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, JapanDepartment of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, JapanDepartment of Preventive Medicine and Public Health, National Defense Medical College, Tokorozawa 359-8513, JapanDepartment of Preventive Medicine and Public Health, National Defense Medical College, Tokorozawa 359-8513, JapanDepartment of Preventive Medicine and Public Health, National Defense Medical College, Tokorozawa 359-8513, JapanDepartment of International Island and Community Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, JapanDepartment of Health and Welfare System, College of Nursing Art and Science, University of Hyogo, Akashi 673-8588, JapanDepartment of Preventive Medicine, Faculty of Medicine, Saga University, Saga 849-8501, JapanDepartment of Preventive Medicine, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, JapanDepartment of Pharmacy, Faculty of Medicine, The University of Tokyo Hospital, The University of Tokyo, Tokyo 113-8655, JapanDepartment of Preventive Medicine and Public Health, National Defense Medical College, Tokorozawa 359-8513, JapanDepartment of Preventive Medicine, Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8503, JapanDepartment of International Island and Community Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, JapanDepartment of Preventive Medicine, Faculty of Medicine, Saga University, Saga 849-8501, JapanDepartment of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanDepartment of Preventive Medicine, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, JapanDepartment of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, JapanDepartment of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, JapanBackground: Renal hypouricemia (RHUC) is characterized by a low serum uric acid (SUA) level and high fractional excretion of uric acid (FE<sub>UA</sub>). Further studies on FE<sub>UA</sub> 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<sub>UA</sub> data. The effects of NFV-<i>URAT1</i> on FE<sub>UA</sub> 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<sub>UA</sub> and decreased SUA, enabling FE<sub>UA</sub> and SUA levels to be estimated. Conversely, FE<sub>UA</sub> 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<sub>UA</sub> 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.https://www.mdpi.com/2227-9059/9/8/1012<i>URAT1/SLC22A12</i>renal hypouricemia (RHUC)serum uric acid (SUA)fractional excretion of uric acid (FE<sub>UA</sub>)

Similar Items