{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T04:19:55Z","timestamp":1777695595808,"version":"3.51.4"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T00:00:00Z","timestamp":1660262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000882","name":"Brain Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000882","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Wernicke\u2013Korsakoff 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Thirty non-synonymous variants were identified in the discovery cohort and, after filtering, 23 were taken forward and genotyped in the case\u2013control 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\u2009=\u20095.7 \u00d7 10\u221211).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/alcalc\/agac032","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T20:07:38Z","timestamp":1660248458000},"page":"581-588","source":"Crossref","is-referenced-by-count":7,"title":["SLC19A1 Genetic Variation Leads to Altered Thiamine Diphosphate Transport: Implications for the Risk of Developing Wernicke\u2013Korsakoff\u2019s Syndrome"],"prefix":"10.1093","volume":"57","author":[{"given":"Niamh L","family":"O\u2019Brien","sequence":"first","affiliation":[{"name":"Molecular Psychiatry Laboratory , Division of Psychiatry, University College London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgia","family":"Quadri","sequence":"additional","affiliation":[{"name":"Molecular Psychiatry Laboratory , Division of Psychiatry, University College London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iain","family":"Lightley","sequence":"additional","affiliation":[{"name":"Centre for Biomarker Research , University of Huddersfield, Huddersfield, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally I","family":"Sharp","sequence":"additional","affiliation":[{"name":"Molecular Psychiatry Laboratory , Division of Psychiatry, University College London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Guerrini","sequence":"additional","affiliation":[{"name":"Erith Health Centre , South London and Maudsley NHS Foundation Trust, London, UK"},{"name":"Institute of Psychiatry , Psychology and Neuroscience, King's College London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iain","family":"Smith","sequence":"additional","affiliation":[{"name":"Alcohol Related Brain Injury Team , Stirling, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathis","family":"Heydtmann","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology , Dumfries & Galloway Royal Infirmary, Cargenbridge, Dumfries, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marsha Y","family":"Morgan","sequence":"additional","affiliation":[{"name":"UCL Institute for Liver & Digestive Health , Division of Medicine, Royal Free Campus, University College London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allan D","family":"Thomson","sequence":"additional","affiliation":[{"name":"Molecular Psychiatry Laboratory , Division of Psychiatry, University College London, UK"},{"name":"Institute of Psychiatry , Psychology and Neuroscience, King's College London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas J","family":"Bass","sequence":"additional","affiliation":[{"name":"Molecular Psychiatry Laboratory , Division of Psychiatry, University College London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick C","family":"McHugh","sequence":"additional","affiliation":[{"name":"Centre for Biomarker Research , University of Huddersfield, Huddersfield, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"McQuillin","sequence":"additional","affiliation":[{"name":"Molecular Psychiatry Laboratory , Division of Psychiatry, University College London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,8,12]]},"reference":[{"key":"2022091207510211000_ref1","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat Methods"},{"key":"2022091207510211000_ref2","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.biocel.2008.04.005","article-title":"Transketolase: observations in alcohol-related brain damage research","volume":"41","author":"Alexander-Kaufman","year":"2009","journal-title":"Int J Biochem Cell Biol"},{"key":"2022091207510211000_ref3","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1111\/j.1530-0277.2007.00437.x","article-title":"Cerebellar vermis proteome of chronic alcoholic individuals","volume":"31","author":"Alexander-Kaufman","year":"2007","journal-title":"Alcohol Clin Exp Res"},{"key":"2022091207510211000_ref4","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/sj.mp.4001741","article-title":"Differential protein expression in the prefrontal white matter of human alcoholics: a proteomics study","volume":"11","author":"Alexander-Kaufman","year":"2006","journal-title":"Mol Psychiatry"},{"key":"2022091207510211000_ref5","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/nature09522","article-title":"Pericytes regulate the blood-brain barrier","volume":"468","author":"Armulik","year":"2010","journal-title":"Nature"},{"key":"2022091207510211000_ref6","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1093\/rheumatology\/ken073","article-title":"Reduced folate carrier polymorphism determines methotrexate uptake by B cells and CD4+ T cells","volume":"47","author":"Baslund","year":"2008","journal-title":"Rheumatology"},{"key":"2022091207510211000_ref7","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1056\/NEJM197712222972503","article-title":"Abnormality of a thiamine-requiring enzyme in patients with Wernicke-Korsakoff syndrome","volume":"297","author":"Blass","year":"1977","journal-title":"N Engl J Med"},{"key":"2022091207510211000_ref8","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1006\/geno.1996.0124","article-title":"Molecular cloning of tissue-specific transcripts of a transketolase-related gene: implications for the evolution of new vertebrate genes","volume":"32","author":"Coy","year":"1996","journal-title":"Genomics"},{"key":"2022091207510211000_ref9","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1097\/00008571-200411000-00004","article-title":"Contribution of common polymorphisms in reduced folate carrier and \u03b3-glutamylhydrolase to methotrexate polyglutamate levels in patients with rheumatoid arthritis","volume":"14","author":"Dervieux","year":"2004","journal-title":"Pharmacogenetics"},{"key":"2022091207510211000_ref10","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/sj.tpj.6500438","article-title":"Reduced folate carrier-1 80G&gt;a polymorphism affects methotrexate treatment outcome in rheumatoid arthritis","volume":"7","author":"Drozdzik","year":"2007","journal-title":"Pharmacogenomics J"},{"key":"2022091207510211000_ref11","volume-title":"The Genetics of Alcohol Metabolism: Role of Alcohol Dehydrogenase and Aldehyde Dehydrogenase Variants. Alcohol Res Heal 30: 5","author":"Edenberg","year":"2007"},{"key":"2022091207510211000_ref12","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"\u2018Mini-mental state\u2019. A practical method for grading the cognitive state of patients for the clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J Psychiatr Res"},{"key":"2022091207510211000_ref13","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/ajmg.b.30194","article-title":"Direct genomic PCR sequencing of the high affinity thiamine transporter (SLC19A2) gene identifies three genetic variants in Wernicke Korsakoff syndrome (WKS)","volume":"137","author":"Guerrini","year":"2005","journal-title":"Am J Med Genet - Neuropsychiatr Genet"},{"key":"2022091207510211000_ref14","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1136\/jnnp.49.4.341","article-title":"Clinical signs in the Wernicke-Korsakoff complex: a retrospective analysis of 131 cases diagnosed at necropsy","volume":"49","author":"Harper","year":"1986","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2022091207510211000_ref15","doi-asserted-by":"crossref","first-page":"35108","DOI":"10.1038\/srep35108","article-title":"Analysis of the brain mural cell transcriptome","volume":"6","author":"He","year":"2016","journal-title":"Sci Rep"},{"key":"2022091207510211000_ref16","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.3389\/fpsyg.2018.02618","article-title":"Identification and evaluation of neuropsychological tools used in the assessment of alcohol-related cognitive impairment: a systematic review","volume":"9","author":"Heirene","year":"2018","journal-title":"Front Psychol"},{"key":"2022091207510211000_ref17","first-page":"701","article-title":"Dual system of intestinal thiamine transport in humans","volume":"99","author":"Hoyumpa","year":"1982","journal-title":"J Lab Clin Med"},{"key":"2022091207510211000_ref18","first-page":"562","article-title":"Common polymorphisms in the folate pathway predict efficacy of combination regimens containing methotrexate and sulfasalazine in early rheumatoid arthritis","volume":"35","author":"James","year":"2008","journal-title":"J Rheumatol"},{"key":"2022091207510211000_ref19","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1056\/NEJMc0809100","article-title":"Mutations in a thiamine-transporter gene and Wernicke\u2019s-like encephalopathy","volume":"360","author":"Kono","year":"2009","journal-title":"N Engl J Med"},{"key":"2022091207510211000_ref20","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1093\/alcalc\/agn118","article-title":"The Korsakoff syndrome: clinical aspects, psychology and treatment","volume":"44","author":"Kopelman","year":"2009","journal-title":"Alcohol Alcohol"},{"key":"2022091207510211000_ref21","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1192\/bjp.139.2.156","article-title":"Wernicke-Korsakoff syndrome in monozygotic twins: a biochemical peculiarity","volume":"139","author":"Leigh","year":"1981","journal-title":"Br J Psychiatry"},{"key":"2022091207510211000_ref22","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nature19057","article-title":"Analysis of protein-coding genetic variation in 60,706 humans","volume":"536","author":"Lek","year":"2016","journal-title":"Nature"},{"key":"2022091207510211000_ref23","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/sj.mp.4000554","article-title":"Association between variants at the GABA(a)\u03b22, GABA(a)\u03b16 and GABA(a)\u03b32 gene cluster and alcohol dependence in a Scottish population","volume":"4","author":"Loh","year":"1999","journal-title":"Mol Psychiatry"},{"key":"2022091207510211000_ref24","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/BF01991782","article-title":"Molecular genetics of transketolase in the pathogenesis of the Wernicke-Korsakoff syndrome","volume":"10","author":"Martin","year":"1995","journal-title":"Metab Brain Dis"},{"key":"2022091207510211000_ref25","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/j.1530-0277.2000.tb04617.x","article-title":"Alcohol and aldehyde dehydrogenase genotypes in Korsakoff syndrome","volume":"24","author":"Matsushita","year":"2000","journal-title":"Alcohol Clin Exp Res"},{"key":"2022091207510211000_ref26","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/S0021-9258(18)54089-8","article-title":"Cloning of human transketolase cDNAs and comparison of the nucleotide sequence of the coding region in Wernicke-Korsakoff and non-Wernicke-Korsakoff individuals","volume":"268","author":"McCool","year":"1993","journal-title":"J Biol Chem"},{"key":"2022091207510211000_ref27","first-page":"1297","article-title":"The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data","author":"McKenna","year":"2010"},{"key":"2022091207510211000_ref28","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1093\/nar\/gkg509","article-title":"SIFT: predicting amino acid changes that affect protein function","volume":"31","author":"Ng","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"2022091207510211000_ref29","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: a tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"key":"2022091207510211000_ref30","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2014"},{"key":"2022091207510211000_ref31","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1006\/mgme.2001.3197","article-title":"Genetic polymorphism (G80A) of reduced folate carrier gene in ethnic populations","volume":"73","author":"Rady","year":"2001","journal-title":"Mol Genet Metab"},{"key":"2022091207510211000_ref32","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1046\/j.1525-1373.2000.22428.x","article-title":"Thiamine intestinal transport and related issues: recent aspects","volume":"224","author":"Rindi","year":"2000","journal-title":"Proc Soc Exp Biol Med"},{"key":"2022091207510211000_ref33","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1016\/S1357-2725(98)00095-8","article-title":"Properties and functions of the thiamin diphosphate dependent enzyme transketolase","volume":"30","author":"Schenk","year":"1998","journal-title":"Int J Biochem Cell Biol"},{"key":"2022091207510211000_ref34","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/S1474-4422(07)70104-7","article-title":"Wernicke\u2019s encephalopathy: new clinical settings and recent advances in diagnosis and management","volume":"6","author":"Sechi","year":"2007","journal-title":"Lancet Neurol"},{"key":"2022091207510211000_ref35","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.0954-6820.1987.tb13042.x","article-title":"Nutrition and alcoholic encephalopathies","volume":"221","author":"Thomson","year":"1987","journal-title":"Acta Med Scand"},{"key":"2022091207510211000_ref36","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0022-510X(82)90145-9","article-title":"Brain lesions in alcoholics. A neuropathological study with clinical correlations","volume":"56","author":"Torvik","year":"1982","journal-title":"J Neurol Sci"},{"key":"2022091207510211000_ref37","first-page":"1","article-title":"The Wernicke-Korsakoff syndrome. A clinical and pathological study of 245 patients, 82 with post-mortem examinations","volume":"7","author":"Victor","year":"1971","journal-title":"Contemp Neurol Ser"},{"key":"2022091207510211000_ref38","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1111\/adb.12141","article-title":"Genetic variants in or near adh1b and adh1c affect susceptibility to alcohol dependence in a british and irish population","volume":"20","author":"Way","year":"2015","journal-title":"Addict Biol"},{"key":"2022091207510211000_ref39","first-page":"134","article-title":"The Montreal Cognitive Assesment (MoCA) as a measure of severity of amnesia in patients with alcohol-related cognitive impairments and Korsakof syndrome","volume":"10","author":"Wester","year":"2013","journal-title":"Clin Neuropsychiatry"},{"key":"2022091207510211000_ref40","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1097\/FPC.0b013e32833eca92","article-title":"SLC19A1 pharmacogenomics summary","volume":"20","author":"Yee","year":"2010","journal-title":"Pharmacogenet Genomics"},{"key":"2022091207510211000_ref41","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/nrneurol.2011.42","article-title":"Clinical and pathological features of alcohol-related brain damage","volume":"7","author":"Zahr","year":"2011","journal-title":"Nat Rev Neurol"},{"key":"2022091207510211000_ref42","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1074\/jbc.M007919200","article-title":"Impact of the reduced folate carrier on the accumulation of active thiamin metabolites in murine leukemia cells","volume":"276","author":"Zhao","year":"2001","journal-title":"J Biol Chem"}],"container-title":["Alcohol and Alcoholism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/alcalc\/article-pdf\/57\/5\/581\/45784828\/agac032.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/alcalc\/article-pdf\/57\/5\/581\/45784828\/agac032.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T07:52:37Z","timestamp":1662969157000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/alcalc\/article\/57\/5\/581\/6661372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,12]]},"references-count":42,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,8,12]]},"published-print":{"date-parts":[[2022,9,10]]}},"URL":"https:\/\/doi.org\/10.1093\/alcalc\/agac032","relation":{},"ISSN":["0735-0414","1464-3502"],"issn-type":[{"value":"0735-0414","type":"print"},{"value":"1464-3502","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,9]]},"published":{"date-parts":[[2022,8,12]]}}}