A Proposal for Practical Diagnosis of Renal Hypouricemia: Evidenced from Genetic Studies of Nonfunctional Variants of URAT1/SLC22A12 among 30,685 Japanese Individuals
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Participants
2.2. Genetics Analysis
2.3. Data Analysis
3. Results
3.1. Distribution of SUA Levels in the Japanese Population
3.2. Frequency of NFV-URAT1 in Hypouricemic Individuals
3.3. Associations between NFV-URAT1 and FEUA or SUA in 2240 Japanese Individuals
3.4. The Effect on FEUA and SUA Levels of the Number of Alleles of NFV-URAT1
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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SUA (mg/dL) | Male | Female | ||
---|---|---|---|---|
Number | Frequency (%) | Number | Frequency (%) | |
0.0–1.0 | 20 | 0.15 | 23 | 0.13 |
1.1–2.0 | 4 | 0.03 | 70 | 0.41 |
2.1–3.0 | 107 | 0.79 | 1093 | 6.40 |
3.1–7.0 | 10,716 | 78.75 | 15,703 | 91.95 |
7.1–8.0 | 1956 | 14.37 | 149 | 0.87 |
8.1–9.0 | 625 | 4.59 | 32 | 0.19 |
9.1– | 179 | 1.32 | 8 | 0.05 |
Total | 13,607 | 100 | 17,078 | 100 |
Male | Female | |||||
---|---|---|---|---|---|---|
Number | Age (year) | BMI (kg/m2) | Number | Age (year) | BMI (kg/m2) | |
Severe hypouricemia (0.0–1.0 mg/dL) | 17 | 56.4 ± 8.1 | 24.2 ± 2.6 | 19 | 55.7 ± 8.1 | 22.1 ± 2.9 |
Moderate hypouricemia (1.1–2.0 mg/dL) | 4 | 53.5 ± 8.3 | 24.1 ± 2.1 | 57 | 50.2 ± 8.4 | 21.3 ± 3.1 |
Mild hypouricemia (2.1–3.0 mg/dL) | 87 | 56.0 ± 8.9 | 22.6 ± 2.9 | 856 | 51.8 ± 9.2 | 21.1 ± 2.9 |
Hypouricemia (≤2.0 mg/dL) | 21 | 55.8 ± 8.2 | 24.2 ± 2.5 | 76 | 51.6 ± 8.7 | 21.5 ± 3.1 |
Hypouricemia + mild hypouricemia (≤3.0 mg/dL) | 108 | 56.0 ± 8.7 | 22.9 ± 2.9 | 932 | 51.8 ± 9.1 | 21.2 ± 2.9 |
Hypouricemic Population (SUA) | Male | Female | ||||||
---|---|---|---|---|---|---|---|---|
Allele Number of NFV-URAT1 | Total | Allele Number of NFV-URAT1 | Total | |||||
0 | 1 | 2 | 0 | 1 | 2 | |||
Severe hypouricemia (0.0–1.0 mg/dL) | 2 (11.8%) | 4 (23.5%) | 11 (64.7%) | 17 (100%) | 0 (0.0%) | 6 (31.6%) | 13 (68.4%) | 19 (100%) |
Moderate hypouricemia (1.1–2.0 mg/dL) | 1 (25.0%) | 3 (75.0%) | 0 (0.0%) | 4 (100%) | 20 (35.1%) | 37 (64.9%) | 0 (0.0%) | 57 (100%) |
Mild hypouricemia (2.1–3.0 mg/dL) | 29 (33.3%) | 58 (66.7%) | 0 (0.0%) | 87 (100%) | 570 (66.6%) | 286 (33.4%) | 0 (0.0%) | 856 (100%) |
Hypouricemia (≤2.0 mg/dL) | 3 (14.3%) | 7 (33.3%) | 11 (52.4%) | 21 (100%) | 20 (26.3%) | 43 (56.6%) | 13(17.1%) | 76 (100%) |
Hypouricemia + mild hypouricemia (≤3.0 mg/dL) | 32 (29.6%) | 65 (60.2%) | 11 (10.2%) | 108 (100%) | 590 (63.3%) | 329 (35.3%) | 13 (1.4%) | 932 (100%) |
Case No. | Sex | Age | NFV-URAT1 | FEUA (%) | SUA (mg/dL) | SCr (mg/dL) | |
---|---|---|---|---|---|---|---|
Number of Alleles | Amino Acid Substitution | ||||||
1 | Female | 69 | 2 | W258X/W258X | 51.32 | 0.5 | 0.6 |
2 | Male | 63 | 2 | W258X/W258X | 60.71 | 0.7 | 0.8 |
3 | Female | 68 | 2 | W258X/W258X | 40.55 | 0.8 | 0.7 |
4 | Male | 57 | 2 | W258X/W258X | 24.52 | 0.8 | 1.0 |
5 | Female | 45 | 1 | W258X/ | 12.08 | 2.3 | 0.6 |
6 | Female | 56 | 1 | W258X/ | 5.67 | 2.4 | 0.8 |
7 | Male | 69 | 1 | W258X/ | 7.80 | 2.4 | 0.7 |
8 | Female | 61 | 1 | W258X/ | 6.04 | 2.5 | 0.5 |
9 | Female | 51 | 1 | W258X/ | 6.40 | 2.6 | 0.6 |
10 | Female | 70 | 1 | W258X/ | 6.97 | 2.6 | 0.6 |
11 | Female | 68 | 1 | W258X/ | 2.17 | 2.8 | 0.6 |
12 | Female | 55 | 1 | W258X/ | 10.41 | 2.9 | 0.7 |
13 | Female | 41 | 1 | W258X/ | 11.12 | 2.9 | 0.4 |
14 | Male | 69 | 1 | W258X/ | 12.51 | 3.0 | 0.9 |
15 | Male | 55 | 1 | W258X/ | 8.19 | 3.0 | 0.9 |
16 | Female | 46 | 1 | R90H/ | 6.55 | 3.0 | 0.5 |
17 | Female | 65 | 0 | 12.45 | 2.0 | 0.5 | |
18 | Male | 54 | 0 | 4.07 | 2.3 | 0.6 | |
19 | Female | 61 | 0 | 14.75 | 2.3 | 0.5 | |
20 | Female | 62 | 0 | 3.40 | 2.5 | 0.5 | |
21 | Female | 45 | 0 | 3.10 | 2.6 | 0.6 | |
22 | Female | 71 | 0 | 12.32 | 2.6 | 0.6 | |
23 | Male | 52 | 0 | 4.91 | 2.6 | 0.7 | |
24 | Female | 50 | 0 | 2.94 | 2.7 | 0.6 | |
25 | Female | 54 | 0 | 6.16 | 2.7 | 0.6 | |
26 | Female | 52 | 0 | 2.05 | 2.7 | 0.6 | |
27 | Female | 62 | 0 | 9.51 | 2.8 | 0.5 | |
28 | Female | 41 | 0 | 7.86 | 2.8 | 0.6 | |
29 | Female | 62 | 0 | 11.76 | 2.8 | 0.5 | |
30 | Female | 58 | 0 | 12.11 | 2.8 | 0.6 | |
31 | Female | 47 | 0 | 6.77 | 2.8 | 0.7 | |
32 | Female | 43 | 0 | 8.11 | 2.8 | 0.5 | |
33 | Female | 41 | 0 | 8.17 | 2.8 | 0.6 | |
34 | Female | 60 | 0 | 5.88 | 2.8 | 0.7 | |
35 | Male | 59 | 0 | 16.86 | 2.8 | 0.8 | |
36 | Female | 51 | 0 | 5.27 | 2.8 | 0.7 | |
37 | Female | 58 | 0 | 12.61 | 2.9 | 0.5 | |
38 | Female | 43 | 0 | 6.64 | 2.9 | 0.7 | |
39 | Female | 47 | 0 | 7.90 | 2.9 | 0.6 | |
40 | Female | 68 | 0 | 8.14 | 2.9 | 0.7 | |
41 | Female | 72 | 0 | 14.10 | 2.9 | 0.4 | |
42 | Female | 52 | 0 | 5.91 | 3.0 | 0.6 | |
43 | Female | 63 | 0 | 6.07 | 3.0 | 0.5 | |
44 | Female | 51 | 0 | 8.29 | 3.0 | 0.5 | |
45 | Female | 69 | 0 | 8.17 | 3.0 | 0.5 | |
46 | Female | 47 | 0 | 8.15 | 3.0 | 0.6 | |
47 | Female | 74 | 0 | 3.34 | 3.0 | 0.6 | |
48 | Female | 59 | 0 | 10.43 | 3.0 | 0.6 | |
49 | Female | 50 | 0 | 8.68 | 3.0 | 0.6 | |
50 | Female | 60 | 0 | 9.96 | 3.0 | 0.6 | |
51 | Female | 56 | 0 | 7.68 | 3.0 | 0.6 | |
52 | Female | 64 | 0 | 4.17 | 3.0 | 0.6 |
Male | Female | ||||
---|---|---|---|---|---|
Partial Regression Coefficient | p Value | Partial Regression Coefficient | p Value | ||
FEUA | β0 | 3.94 | 0 | 5.40 | 1.61 × 10−249 |
β1 | 2.63 | 4.04 × 10−20 | ― | ― | |
β2 | 38.68 | 1.35 × 10−108 | 40.54 | 2.15 × 10−79 | |
SUA | β0 | 6.10 | 0 | 4.56 | 0 |
β1 | –1.93 | 6.56 × 10−45 | −1.25 | 1.53 × 10−7 | |
β2 | –5.35 | 2.39 × 10−12 | −3.91 | 2.97 × 10−8 |
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Kawamura, Y.; Nakayama, A.; Shimizu, S.; Toyoda, Y.; Nishida, Y.; Hishida, A.; Katsuura-Kamano, S.; Shibuya, K.; Tamura, T.; Kawaguchi, M.; Suzuki, S.; Iwasawa, S.; Nakashima, H.; Ibusuki, R.; Uemura, H.; Hara, M.; Takeuchi, K.; Takada, T.; Tsunoda, M.; Arisawa, K.; Takezaki, T.; Tanaka, K.; Ichida, K.; Wakai, K.; Shinomiya, N.; Matsuo, H. 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, 9, 1012. https://doi.org/10.3390/biomedicines9081012
Kawamura Y, Nakayama A, Shimizu S, Toyoda Y, Nishida Y, Hishida A, Katsuura-Kamano S, Shibuya K, Tamura T, Kawaguchi M, Suzuki S, Iwasawa S, Nakashima H, Ibusuki R, Uemura H, Hara M, Takeuchi K, Takada T, Tsunoda M, Arisawa K, Takezaki T, Tanaka K, Ichida K, Wakai K, Shinomiya N, Matsuo H. 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; 9(8):1012. https://doi.org/10.3390/biomedicines9081012
Chicago/Turabian StyleKawamura, Yusuke, 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, and Hirotaka Matsuo. 2021. "A Proposal for Practical Diagnosis of Renal Hypouricemia: Evidenced from Genetic Studies of Nonfunctional Variants of URAT1/SLC22A12 among 30,685 Japanese Individuals" Biomedicines 9, no. 8: 1012. https://doi.org/10.3390/biomedicines9081012