RT Journal Article
T1 Identification of a functional variant in the KIF5A-CYP27B1-METTL1-FAM119B locus associated with multiple sclerosis.
A1 Alcina, Antonio
A1 Fedetz, María
A1 Fernández, Óscar
A1 Saiz, Albert
A1 Izquierdo, Guillermo
A1 Lucas, Miguel
A1 Leyva-Fernández, Laura
A1 García-León, Juan Antonio
A1 Abad-Grau, María del Mar
A1 Alloza, Iraide
A1 Antigüedad, Alfredo
A1 Garcia-Barcina, María Jesús
A1 Vandenbroeck, Koen
A1 Varadé, Jezabel
A1 de la Hera, Belén
A1 Arroyo, Rafael
A1 Comabella, Manuel
A1 Montalban, Xavier
A1 Petit-Marty, Natalia
A1 Navarro, Arcadi
A1 Otaegui, David
A1 Olascoaga, Javier
A1 Blanco, Yolanda
A1 Urcelay, Elena
A1 Matesanz, Fuencisla
K1 Esclerosis múltiple
AB Background and aim: Several studies have highlighted the association of the 12q13.3-12q14.1 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.Methods: 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.Results: 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 FAM119B, AVIL, TSFM, TSPAN31 and CYP27B1 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.Conclusions: 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 12q13.3-12q14.1 region with MS.
PB BMJ Journals
YR 2013
FD 2013-01
LK https://hdl.handle.net/10630/34653
UL https://hdl.handle.net/10630/34653
LA eng
NO Antonio Alcina, Maria Fedetz, Oscar Fernández, Albert Saiz, Guillermo Izquierdo, Miguel Lucas, Laura Leyva, Juan-Antonio García-León, María Del Mar Abad-Grau, Iraide Alloza, Alfredo Antigüedad, María J Garcia-Barcina, Koen Vandenbroeck, Jezabel Varadé, Belén de la Hera, Rafael Arroyo, Manuel Comabella, Xavier Montalban, Natalia Petit-Marty, Arcadi Navarro, David Otaegui, Javier Olascoaga, Yolanda Blanco, Elena Urcelay, Fuencisla Matesanz. Identification of a functional variant in the KIF5A-CYP27B1-METTL1-FAM119B locus associated with multiple Sclerosis. J Med Genet. 2013 Jan;50(1):25-33. doi: 10.1136/jmedgenet-2012-101085. Epub 2012 Nov 17.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 28 ene 2026