RT Journal Article
T1 Genome-wide pathway analysis identifies VEGF pathway association with oral ulceration in systemic lupus erythematosus.
A1 Aterido, Adria
A1 Julia, Antonio
A1 Carreira, Patricia
A1 Blanco, Ricardo
A1 Lopez-Longo, Jose Javier
A1 Venegas, Jose Javier Perez
A1 Olivé, Alex
A1 Andreu, Jose Luis
A1 Aguirre-Zamorano, Maria Angeles
A1 Vela, Paloma
A1 Nolla, Joan M
A1 Marenco-de la Fuente, Jose Luis
A1 Zea, Antonio
A1 Pego, Jose Maria
A1 Freire, Mercedes
A1 Diez, Elvira
A1 Lopez-Lasanta, Maria
A1 Lopez-Corbeto, Mireia
A1 Palau, Nuria
A1 Tortosa, Raul
A1 Gelpi, Josep Lluis
A1 Absher, Devin
A1 Myers, Richard M
A1 Fernandez-Nebro, Antonio
A1 Marsal, Sara
K1 Clinical phenotypes
K1 Genetics
K1 Genome-wide pathway analysis
K1 Oral ulceration
K1 Systemic lupus erythematosus
K1 Área de Gestión Sanitaria de Jerez, Costa Noroeste y Sierra de Cádiz
K1 Área de Gestión Sanitaria Sur de Sevilla
AB Systemic lupus erythematosus (SLE) is a genetically complex rheumatic disease characterized by heterogeneous clinical manifestations of unknown etiology. Recent studies have suggested the existence of a genetic basis for SLE heterogeneity. The objective of the present study was to identify new genetic variation associated with the clinically relevant phenotypes in SLE. A two-stage pathway-based approach was used to identify the genetic variation associated with the main clinical phenotypes in SLE. In the discovery stage, 482 SLE patients were genotyped using Illumina Human Quad610 microarrays. Association between 798 reference genetic pathways from the Molecular Signatures Database and 11 SLE phenotypes was tested using the set-based method implemented in PLINK software. Pathways significantly associated after multiple test correction were subsequently tested for replication in an independent cohort of 425 SLE patients. Using an in silico approach, we analyzed the functional effects of common SLE therapies on the replicated genetic pathways. The association of known SLE risk variants with the development of the clinical phenotypes was also analyzed. In the discovery stage, we found a significant association between the vascular endothelial growth factor (VEGF) pathway and oral ulceration (P value for false discovery rate (P FDR)  The present study has identified VEGF genetic pathway association with the risk of oral ulceration in SLE. New therapies targeting the VEGF pathway could be more effective in reducing the severity of this phenotype. These findings represent a first step towards the understanding of the genetic basis of phenotype heterogeneity in SLE.
PB BioMed Central
YR 2017
FD 2017-06-15
LK http://hdl.handle.net/10668/11306
UL http://hdl.handle.net/10668/11306
LA en
NO Aterido A, Julià A, Carreira P, Blanco R, López-Longo JJ, Venegas JJP, et al. Genome-wide pathway analysis identifies VEGF pathway association with oral ulceration in systemic lupus erythematosus. Arthritis Res Ther. 2017 Jun 15;19(1):138
DS RISalud
RD Apr 18, 2025