{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:18:38Z","timestamp":1790813918415,"version":"4.1.0"},"reference-count":42,"publisher":"BMJ","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2012,10,10]]},"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:sec>\n                  <jats:title>Background and aim<\/jats:title>\n                  <jats:p>Several studies have highlighted the association of the 12q13.3\u201312q14.1 region with coeliac disease, type 1 diabetes, rheumatoid arthritis and multiple sclerosis (MS); however, the causal variants underlying diseases are still unclear. The authors sought to identify the functional variant of this region associated with MS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Tag-single nucleotide polymorphism (SNP) analysis of the associated region encoding 15 genes was performed in 2876 MS patients and 2910 healthy Caucasian controls together with expression regulation analyses.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>rs6581155, which tagged 18 variants within a region where 9 genes map, was sufficient to model the association. This SNP was in total linkage disequilibrium (LD) with other polymorphisms that associated with the expression levels of <jats:italic>FAM119B, AVIL, TSFM, TSPAN31<\/jats:italic> and <jats:italic>CYP27B1<\/jats:italic> genes in different expression quantitative trait loci studies. Functional annotations from Encyclopedia of DNA Elements (ENCODE) showed that six out of these rs6581155-tagged-SNPs were located in regions with regulatory potential and only one of them, rs10877013, exhibited allele-dependent (ratio A\/G=9.5-fold) and orientation-dependent (forward\/reverse=2.7-fold) enhancer activity as determined by luciferase reporter assays. This enhancer is located in a region where a long-range chromatin interaction among the promoters and promoter-enhancer of several genes has been described, possibly affecting their expression simultaneously.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study determines a functional variant which alters the enhancer activity of a regulatory element in the locus affecting the expression of several genes and explains the association of the 12q13.3\u201312q14.1 region with MS.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmedgenet-2012-101085","type":"journal-article","created":{"date-parts":[[2012,11,17]],"date-time":"2012-11-17T21:30:06Z","timestamp":1353187806000},"page":"25-33","source":"Crossref","is-referenced-by-count":68,"title":["Identification of a functional variant in the <i>KIF5A-CYP27B1-METTL1-FAM119B<\/i> locus associated with multiple sclerosis"],"prefix":"10.1136","volume":"50","author":[{"given":"Antonio","family":"Alcina","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Immunology Instituto de Parasitolog\u00eda y Biomedicina \u2018L\u00f3pez Neyra\u2019, Consejo Superior de Investigaciones Cient\u00edficas (IPBLN-CSIC), Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Fedetz","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Immunology Instituto de Parasitolog\u00eda y Biomedicina \u2018L\u00f3pez Neyra\u2019, Consejo Superior de Investigaciones Cient\u00edficas (IPBLN-CSIC), Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d3scar","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Servicio de Neurolog\u00eda, Instituto de Neurociencias Cl\u00ednicas, Hospital Regional Universitario Carlos Haya, M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Saiz","sequence":"additional","affiliation":[{"name":"Neurology Service, Hospital Clinic and I. d\u00b4Investigaci\u00f3 Biom\u00e8dica Pi iSunyer (IDIBAPS), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Izquierdo","sequence":"additional","affiliation":[{"name":"Unidad de Esclerosis M\u00faltiple, Hospital Virgen Macarena, Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Lucas","sequence":"additional","affiliation":[{"name":"Servicio de Biolog\u00eda Molecular, Hospital Virgen Macarena, Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Leyva","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n, Instituto de Neurociencias Cl\u00ednicas, Hospital Regional Universitario Carlos Haya, M\u00e1laga, 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