title: Identification of a two-loci epistatic interaction associated with susceptibility to rheumatoid arthritis through reverse engineering and multifactor dimensionality reduction.
abstract: Altered synovial fibroblast (SF) transcriptional activity is a key factor in the disease progression of rheumatoid arthritis (RA). To determine the transcriptional regulatory network associated with SF response to an RA proinflammatory stimulus we applied a CARRIE reverse engineering approach to microarray gene expression data from SFs treated with RA synovial fluid. The association of the inferred gene network with RA susceptibility was further analyzed by a case-control study of promoter single-nucleotide polymorphisms, and the presence of epistatic interactions was determined using the multifactor dimensionality reduction methodology. Our findings suggest that a specific NF-kappaB transcriptional regulatory network of 13 genes is associated with SF response to RA proinflammatory stimulus and identify a significant epistatic association of two of its genes, IL6 and IL4I1, with RA susceptibility.
authors.affiliation: Unitat de Recerca de Reumatologia, Institut de Recerca Hospital Universitari Vall d'Hebron, UAB, 08035 Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Julià
authors.forename: Jason
authors.initials: J
authors.lastname: Moore
authors.forename: Laia
authors.initials: L
authors.lastname: Miquel
authors.forename: Cayetano
authors.initials: C
authors.lastname: Alegre
authors.forename: Pere
authors.initials: P
authors.lastname: Barceló
authors.forename: Marylyn
authors.initials: M
authors.lastname: Ritchie
authors.forename: Sara
authors.initials: S
authors.lastname: Marsal
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D004843:Epistasis, Genetic; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling; D005818:Genetic Engineering; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D013582:Synovial Fluid / Q000502:physiology; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism
chemical_list: D005819:Genetic Markers; D016328:NF-kappa B