دورية أكاديمية
SLC19A1 Genetic Variation Leads to Altered Thiamine Diphosphate Transport: Implications for the Risk of Developing Wernicke-Korsakoff's Syndrome.
| العنوان: | SLC19A1 Genetic Variation Leads to Altered Thiamine Diphosphate Transport: Implications for the Risk of Developing Wernicke-Korsakoff's Syndrome. |
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| المؤلفون: | O'Brien NL; Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, UK., Quadri G; Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, UK., Lightley I; Centre for Biomarker Research, University of Huddersfield, Huddersfield, UK., Sharp SI; Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, UK., Guerrini I; Erith Health Centre, South London and Maudsley NHS Foundation Trust, London, UK.; Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK., Smith I; Alcohol Related Brain Injury Team, Stirling, UK., Heydtmann M; Department of Gastroenterology, Dumfries & Galloway Royal Infirmary, Cargenbridge, Dumfries, UK., Morgan MY; UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, UK., Thomson AD; Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, UK.; Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK., Bass NJ; Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, UK., McHugh PC; Centre for Biomarker Research, University of Huddersfield, Huddersfield, UK., McQuillin A; Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, UK. |
| المصدر: | Alcohol and alcoholism (Oxford, Oxfordshire) [Alcohol Alcohol] 2022 Sep 10; Vol. 57 (5), pp. 581-588. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 8310684 Publication Model: Print Cited Medium: Internet ISSN: 1464-3502 (Electronic) Linking ISSN: 07350414 NLM ISO Abbreviation: Alcohol Alcohol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2003- > : Oxford : Oxford University Press Original Publication: Oxford ; New York : Pergamon Press, c1983- |
| مواضيع طبية MeSH: | Alcoholism*/complications , Korsakoff Syndrome*/complications , Reduced Folate Carrier Protein*/genetics , Thiamine Deficiency*/genetics, Ethanol ; Folic Acid ; Genetic Variation/genetics ; HEK293 Cells ; Humans ; Thiamine ; Thiamine Pyrophosphate/metabolism |
| مستخلص: | Aims: Wernicke-Korsakoff syndrome (WKS) is commonly associated with chronic alcohol misuse, a condition known to have multiple detrimental effects on thiamine metabolism. This study was conducted to identify genetic variants that may contribute to the development of WKS in individuals with alcohol dependence syndrome through alteration of thiamine transport into cells. Methods: Exome sequencing data from a panel of genes related to alcohol metabolism and thiamine pathways were analysed in a discovery cohort of 29 individuals with WKS to identify possible genetic risk variants associated with its development. Variant frequencies in this discovery cohort were compared with European frequencies in the Genome Aggregation Database browser, and those present at significantly higher frequencies were genotyped in an additional cohort of 87 alcohol-dependent cases with WKS and 197 alcohol-dependent cognitively intact controls. Results: Thirty non-synonymous variants were identified in the discovery cohort and, after filtering, 23 were taken forward and genotyped in the case-control cohort. Of these SLC19A1:rs1051266:G was nominally associated with WKS. SLC19A1 encodes the reduced folate carrier, a major transporter for physiological folate in plasma; rs1051266 is reported to impact folate transport. Thiamine pyrophosphate (TPP) efflux was significantly decreased in HEK293 cells, stably transfected with rs1051266:G, under thiamine deficient conditions when compared with the efflux from cells transfected with rs1051266:A (P = 5.7 × 10-11). Conclusion: This study provides evidence for the role of genetic variation in the SLC19A1 gene, which may contribute to the development of WKS in vivo through modulation of TPP transport in cells. (© The Author(s) 2022. Medical Council on Alcohol and Oxford University Press. All rights reserved.) |
| معلومات مُعتمدة: | Brain Research Foundation |
| المشرفين على المادة: | 0 (Reduced Folate Carrier Protein) 0 (SLC19A1 protein, human) 3K9958V90M (Ethanol) 935E97BOY8 (Folic Acid) Q57971654Y (Thiamine Pyrophosphate) X66NSO3N35 (Thiamine) |
| تواريخ الأحداث: | Date Created: 20220811 Date Completed: 20220913 Latest Revision: 20220922 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1093/alcalc/agac032 |
| PMID: | 35952336 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1464-3502 |
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| DOI: | 10.1093/alcalc/agac032 |