Gene expression and chromosomal location for susceptibility to Sjögren's syndrome

Primary Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease affecting mainly the exocrine glands. Its physio-pathology is poorly understood and most of the knowledge has been related to the inflammatory component. The aim of this work was to evaluate gene expression profiling i...

Full description

Autores:
Tipo de recurso:
Fecha de publicación:
2009
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/22251
Acceso en línea:
https://doi.org/10.1016/j.jaut.2009.05.001
https://repository.urosario.edu.co/handle/10336/22251
Palabra clave:
Complementary DNA
Genomic DNA
Interferon
RNA
Adult
Aged
Apoptosis
Article
Chromosomal localization
Controlled study
DNA microarray
Epithelium cell
Female
Gene amplification
Gene expression profiling
Gene expression regulation
Gene locus
Gene overexpression
Genetic susceptibility
Genome analysis
Human
Human cell
Major clinical study
Microsatellite marker
Priority journal
Reverse transcription polymerase chain reaction
RNA hybridization
Salivary gland
Signal transduction
Sjoegren syndrome
Adult
Aged
Alleles
Epithelial Cells
Female
Gene Expression
Gene Expression Profiling
Gene Frequency
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Microsatellite Repeats
Middle Aged
Salivary Glands
Sjogren's Syndrome
Apoptosis
Cdna microarray
Epithelial cells
Genome-wide association study
Interferon
Sjögren's syndrome
Human
Chromosomes
Rights
License
Abierto (Texto Completo)
Description
Summary:Primary Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease affecting mainly the exocrine glands. Its physio-pathology is poorly understood and most of the knowledge has been related to the inflammatory component. The aim of this work was to evaluate gene expression profiling in fractions enriched in epithelial cells from labial salivary glands (LSGs) of patients with primary SS and identify chromosomal regions harboring susceptibility genes expressed in epithelial cells. A combined approach of gene expression and genome-wide association study was used. Enriched epithelial cell fractions were obtained from LSGs of patients and controls. Amplified total RNA was labeled and hybridized to 10K cDNA microarrays. Results were normalized and subjected to statistical and functional analysis. A genome-wide microsatellite screen at 10 cM resolution (393 markers) was performed. In salivary gland-epithelial cells from patients 528 genes were expressed differentially in comparison to controls. Pathways not previously linked to disease were found to be altered. Twenty-eight and 15 genes associated with apoptosis were up-regulated and down regulated, respectively. Interferon-related genes, most of which participated in interferon signaling, were also found to be up-regulated. From the genome-wide screen, 6 markers showed evidence of highly significant association with the disease. Of these, five loci harbor genes differentially expressed in patients LSG-epithelial cells. Our results show that in enriched gland-epithelial cells of pSS, both pro-apoptotic/anti-apoptotic and interferon signaling inhibition/stimulation balances may occur. Genes found over-expressed in epithelial cells are candidates for disease susceptibility. © 2009 Elsevier Ltd. All rights reserved.