Plasma and Urinary Metabolomic Analysis of Gout and Asymptomatic Hyperuricemia and Profiling of Potential Biomarkers: A Pilot Study
Gout results from monosodium urate deposition caused by hyperuricemia, but most individuals with hyperuricemia remain asymptomatic. The pathogenesis of gout remains uncertain. To identify potential biomarkers distinguishing gout from asymptomatic hyperuricemia, we conducted a genetic analysis of ura...
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MDPI AG
2024-01-01
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| Online Access: | https://www.mdpi.com/2227-9059/12/2/300 |
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| author | Yuki Ohashi Hiroshi Ooyama Hideki Makinoshima Tappei Takada Hirotaka Matsuo Kimiyoshi Ichida |
| author_facet | Yuki Ohashi Hiroshi Ooyama Hideki Makinoshima Tappei Takada Hirotaka Matsuo Kimiyoshi Ichida |
| author_sort | Yuki Ohashi |
| collection | DOAJ |
| description | Gout results from monosodium urate deposition caused by hyperuricemia, but most individuals with hyperuricemia remain asymptomatic. The pathogenesis of gout remains uncertain. To identify potential biomarkers distinguishing gout from asymptomatic hyperuricemia, we conducted a genetic analysis of urate transporters and metabolomic analysis as a proof-of-concept study, including 33 patients with gout and 9 individuals with asymptomatic hyperuricemia. The variant allele frequencies of rs72552713, rs2231142, and rs3733591, which are related to serum urate levels (SUA) and gout, did not differ between the gout and asymptomatic hyperuricemia groups. In metabolomic analysis, the levels of citrate cycle intermediates, especially 2-ketoglutarate, were higher in patients with gout than in those with asymptomatic hyperuricemia (fold difference = 1.415, <i>p</i> = 0.039). The impact on the TCA cycle was further emphasized in high-risk gout (SUA ≥ 9.0 mg/dL). Of note, urinary nicotinate was the most prominent biomarker differentiating high-risk gout from asymptomatic hyperuricemia (fold difference = 6.515, <i>p</i> = 0.020). Although urate transporters play critical roles in SUA elevation and promote hyperuricemia, this study suggests that the progression from asymptomatic hyperuricemia to gout might be closely related to other genetic and/or environmental factors affecting carbohydrate metabolism and urinary urate excretion. |
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| language | English |
| last_indexed | 2024-03-07T22:41:24Z |
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| spelling | doaj.art-219815994aeb497cadffb363e407f2682024-02-23T15:08:25ZengMDPI AGBiomedicines2227-90592024-01-0112230010.3390/biomedicines12020300Plasma and Urinary Metabolomic Analysis of Gout and Asymptomatic Hyperuricemia and Profiling of Potential Biomarkers: A Pilot StudyYuki Ohashi0Hiroshi Ooyama1Hideki Makinoshima2Tappei Takada3Hirotaka Matsuo4Kimiyoshi Ichida5Department of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanRyogoku Higashiguchi Clinic, Tokyo 130-0026, JapanTsuruoka Metabolomics Laboratory, National Cancer Center, Yamagata 997-0052, JapanDepartment of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, JapanDepartment of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Saitama 359-8513, JapanDepartment of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanGout results from monosodium urate deposition caused by hyperuricemia, but most individuals with hyperuricemia remain asymptomatic. The pathogenesis of gout remains uncertain. To identify potential biomarkers distinguishing gout from asymptomatic hyperuricemia, we conducted a genetic analysis of urate transporters and metabolomic analysis as a proof-of-concept study, including 33 patients with gout and 9 individuals with asymptomatic hyperuricemia. The variant allele frequencies of rs72552713, rs2231142, and rs3733591, which are related to serum urate levels (SUA) and gout, did not differ between the gout and asymptomatic hyperuricemia groups. In metabolomic analysis, the levels of citrate cycle intermediates, especially 2-ketoglutarate, were higher in patients with gout than in those with asymptomatic hyperuricemia (fold difference = 1.415, <i>p</i> = 0.039). The impact on the TCA cycle was further emphasized in high-risk gout (SUA ≥ 9.0 mg/dL). Of note, urinary nicotinate was the most prominent biomarker differentiating high-risk gout from asymptomatic hyperuricemia (fold difference = 6.515, <i>p</i> = 0.020). Although urate transporters play critical roles in SUA elevation and promote hyperuricemia, this study suggests that the progression from asymptomatic hyperuricemia to gout might be closely related to other genetic and/or environmental factors affecting carbohydrate metabolism and urinary urate excretion.https://www.mdpi.com/2227-9059/12/2/300gouthyperuricemiauric acidABCG2SLC2A9metabolomics |
| spellingShingle | Yuki Ohashi Hiroshi Ooyama Hideki Makinoshima Tappei Takada Hirotaka Matsuo Kimiyoshi Ichida Plasma and Urinary Metabolomic Analysis of Gout and Asymptomatic Hyperuricemia and Profiling of Potential Biomarkers: A Pilot Study Biomedicines gout hyperuricemia uric acid ABCG2 SLC2A9 metabolomics |
| title | Plasma and Urinary Metabolomic Analysis of Gout and Asymptomatic Hyperuricemia and Profiling of Potential Biomarkers: A Pilot Study |
| title_full | Plasma and Urinary Metabolomic Analysis of Gout and Asymptomatic Hyperuricemia and Profiling of Potential Biomarkers: A Pilot Study |
| title_fullStr | Plasma and Urinary Metabolomic Analysis of Gout and Asymptomatic Hyperuricemia and Profiling of Potential Biomarkers: A Pilot Study |
| title_full_unstemmed | Plasma and Urinary Metabolomic Analysis of Gout and Asymptomatic Hyperuricemia and Profiling of Potential Biomarkers: A Pilot Study |
| title_short | Plasma and Urinary Metabolomic Analysis of Gout and Asymptomatic Hyperuricemia and Profiling of Potential Biomarkers: A Pilot Study |
| title_sort | plasma and urinary metabolomic analysis of gout and asymptomatic hyperuricemia and profiling of potential biomarkers a pilot study |
| topic | gout hyperuricemia uric acid ABCG2 SLC2A9 metabolomics |
| url | https://www.mdpi.com/2227-9059/12/2/300 |
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