The effects of URAT1/SLC22A12 nonfunctional variants, R90H and W258X, on serum uric acid levels and gout/hyperuricemia progression

Scientific Reports
Masayuki SakiyamaNariyoshi Shinomiya

Abstract

Urate transporter 1 (URAT1/SLC22A12), a urate transporter gene, is a causative gene for renal hypouricemia type 1. Among several reported nonsynonymous URAT1 variants, R90H (rs121907896) and W258X (rs121907892) are frequent causative mutations for renal hypouricemia. However, no case-control study has evaluated the relationship between gout and these two variants. Additionally, the effect size of these two variants on serum uric acid (SUA) levels remains to be clarified. Here, 1,993 primary gout patients and 4,902 health examination participants (3,305 males and 1,597 females) were genotyped with R90H and W258X. These URAT1 variants were not observed in any gout cases, while 174 subjects had the URAT1 variant in 2,499 health examination participants, respectively (P = 8.3 × 10(-46)). Moreover, in 4,902 health examination participants, the URAT1 nonfunctional variants significantly reduce the risk of hyperuricemia (P = 6.7 × 10(-19); risk ratio = 0.036 in males). Males, having 1 or 2 nonfunctional variants of URAT1, show a marked decrease of 2.19 or 5.42 mg/dl SUA, respectively. Similarly, females, having 1 or 2 nonfunctional variants, also evidence a decrease of 1.08 or 3.89 mg/dl SUA, respectively. We show that URAT1 nonfuncti...Continue Reading

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Citations

May 14, 2016·Journal of Atherosclerosis and Thrombosis·Hirohito Metoki
Sep 3, 2016·Modern Rheumatology·Hiraku OgataNariyoshi Shinomiya
Nov 16, 2016·Biomolecules·Panagiota PapanagnouMaria Tsironi
Jan 1, 2017·Rheumatology·Tzer-Min KuoYing-Chin Ko
Jul 11, 2019·Annals of the Rheumatic Diseases·Yusuke KawamuraHirotaka Matsuo
Dec 3, 2016·Nucleosides, Nucleotides & Nucleic Acids·Masayuki SakiyamaNariyoshi Shinomiya
Apr 8, 2020·Hypertension in Pregnancy : Official Journal of the International Society for the Study of Hypertension in Pregnancy·Olive P KhaliqThajasvarie Naicker
Jun 2, 2017·Scientific Reports·Masayuki SakiyamaNariyoshi Shinomiya
May 10, 2018·Nature Reviews. Rheumatology·Tanya J MajorTony R Merriman
Apr 29, 2021·Signal Transduction and Targeted Therapy·Zhao HuangYong Tang
Sep 10, 2021·Journal of Clinical Laboratory Analysis·Liting WuWenfang Zhuang

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Methods Mentioned

BETA
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