Functional Characterization of Rare Variants in OAT1/<i>SLC22A6</i> and OAT3/<i>SLC22A8</i> Urate Transporters Identified in a Gout and Hyperuricemia Cohort
The OAT1 (<i>SLC22A6</i>) and OAT3 (<i>SLC22A8</i>) urate transporters are located on the basolateral membrane of the proximal renal tubules, where they ensure the uptake of uric acid from the urine back into the body. In a cohort of 150 Czech patients with primary hyperurice...
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MDPI AG
2022-03-01
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| author | Jiří Vávra Andrea Mančíková Kateřina Pavelcová Lenka Hasíková Jana Bohatá Blanka Stibůrková |
| author_facet | Jiří Vávra Andrea Mančíková Kateřina Pavelcová Lenka Hasíková Jana Bohatá Blanka Stibůrková |
| author_sort | Jiří Vávra |
| collection | DOAJ |
| description | The OAT1 (<i>SLC22A6</i>) and OAT3 (<i>SLC22A8</i>) urate transporters are located on the basolateral membrane of the proximal renal tubules, where they ensure the uptake of uric acid from the urine back into the body. In a cohort of 150 Czech patients with primary hyperuricemia and gout, we examined the coding regions of both genes using PCR amplification and Sanger sequencing. Variants p.P104L (rs11568627) and p.A190T (rs146282438) were identified in the gene for solute carrier family 22 member 6 (<i>SLC22A6</i>) and variants p.R149C (rs45566039), p.V448I (rs11568486) and p.R513Q (rs145474422) in the gene solute carrier family 22 member 8 (<i>SLC22A8</i>). We performed a functional study of these rare non-synonymous variants using the HEK293T cell line. We found that only p.R149C significantly reduced uric acid transport in vitro. Our results could deepen the understanding of uric acid handling in the kidneys and the molecular mechanism of uric acid transport by the OAT family of organic ion transporters. |
| first_indexed | 2024-03-09T12:01:34Z |
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| id | doaj.art-51fca690f87947968790cbab6e029aaa |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T12:01:34Z |
| publishDate | 2022-03-01 |
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| spelling | doaj.art-51fca690f87947968790cbab6e029aaa2023-11-30T23:02:58ZengMDPI AGCells2073-44092022-03-01117106310.3390/cells11071063Functional Characterization of Rare Variants in OAT1/<i>SLC22A6</i> and OAT3/<i>SLC22A8</i> Urate Transporters Identified in a Gout and Hyperuricemia CohortJiří Vávra0Andrea Mančíková1Kateřina Pavelcová2Lenka Hasíková3Jana Bohatá4Blanka Stibůrková5Department of Cell Biology, Faculty of Science, Charles University, Vinicna 7, 128 43 Prague, Czech RepublicDepartment of Staphylococcal and Food-Borne Bacterial Infections, The National Institute of Public Health, Šrobárova 49/48, 100 00 Prague, Czech RepublicInstitute of Rheumatology, Na Slupi 450, 128 00 Prague, Czech RepublicInstitute of Rheumatology, Na Slupi 450, 128 00 Prague, Czech RepublicInstitute of Rheumatology, Na Slupi 450, 128 00 Prague, Czech RepublicInstitute of Rheumatology, Na Slupi 450, 128 00 Prague, Czech RepublicThe OAT1 (<i>SLC22A6</i>) and OAT3 (<i>SLC22A8</i>) urate transporters are located on the basolateral membrane of the proximal renal tubules, where they ensure the uptake of uric acid from the urine back into the body. In a cohort of 150 Czech patients with primary hyperuricemia and gout, we examined the coding regions of both genes using PCR amplification and Sanger sequencing. Variants p.P104L (rs11568627) and p.A190T (rs146282438) were identified in the gene for solute carrier family 22 member 6 (<i>SLC22A6</i>) and variants p.R149C (rs45566039), p.V448I (rs11568486) and p.R513Q (rs145474422) in the gene solute carrier family 22 member 8 (<i>SLC22A8</i>). We performed a functional study of these rare non-synonymous variants using the HEK293T cell line. We found that only p.R149C significantly reduced uric acid transport in vitro. Our results could deepen the understanding of uric acid handling in the kidneys and the molecular mechanism of uric acid transport by the OAT family of organic ion transporters.https://www.mdpi.com/2073-4409/11/7/1063hyperuricemiagoutOAT1OAT3urate transport |
| spellingShingle | Jiří Vávra Andrea Mančíková Kateřina Pavelcová Lenka Hasíková Jana Bohatá Blanka Stibůrková Functional Characterization of Rare Variants in OAT1/<i>SLC22A6</i> and OAT3/<i>SLC22A8</i> Urate Transporters Identified in a Gout and Hyperuricemia Cohort Cells hyperuricemia gout OAT1 OAT3 urate transport |
| title | Functional Characterization of Rare Variants in OAT1/<i>SLC22A6</i> and OAT3/<i>SLC22A8</i> Urate Transporters Identified in a Gout and Hyperuricemia Cohort |
| title_full | Functional Characterization of Rare Variants in OAT1/<i>SLC22A6</i> and OAT3/<i>SLC22A8</i> Urate Transporters Identified in a Gout and Hyperuricemia Cohort |
| title_fullStr | Functional Characterization of Rare Variants in OAT1/<i>SLC22A6</i> and OAT3/<i>SLC22A8</i> Urate Transporters Identified in a Gout and Hyperuricemia Cohort |
| title_full_unstemmed | Functional Characterization of Rare Variants in OAT1/<i>SLC22A6</i> and OAT3/<i>SLC22A8</i> Urate Transporters Identified in a Gout and Hyperuricemia Cohort |
| title_short | Functional Characterization of Rare Variants in OAT1/<i>SLC22A6</i> and OAT3/<i>SLC22A8</i> Urate Transporters Identified in a Gout and Hyperuricemia Cohort |
| title_sort | functional characterization of rare variants in oat1 i slc22a6 i and oat3 i slc22a8 i urate transporters identified in a gout and hyperuricemia cohort |
| topic | hyperuricemia gout OAT1 OAT3 urate transport |
| url | https://www.mdpi.com/2073-4409/11/7/1063 |
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