Genome-wide association studies and gene expression profiles of rheumatoid arthritis
نویسندگان
چکیده
OBJECTIVES The molecular mechanism of rheumatoid arthritis (RA) remains elusive. We conducted a protein-protein interaction network-based integrative analysis of genome-wide association studies (GWAS) and gene expression profiles of RA. METHODS We first performed a dense search of RA-associated gene modules by integrating a large GWAS meta-analysis dataset (containing 5539 RA patients and 20 169 healthy controls), protein interaction network and gene expression profiles of RA synovium and peripheral blood mononuclear cells (PBMCs). Gene ontology (GO) enrichment analysis was conducted by DAVID. The protein association networks of gene modules were generated by STRING. RESULTS For RA synovium, the top-ranked gene module is HLA-A, containing TAP2, HLA-A, HLA-C, TAPBP and LILRB1 genes. For RA PBMCs, the top-ranked gene module is GRB7, consisting of HLA-DRB5, HLA-DRA, GRB7, CD63 and KIT genes. Functional enrichment analysis identified three significant GO terms for RA synovium, including antigen processing and presentation of peptide antigen via major histocompatibility complex class I (false discovery rate (FDR) = 4.86 × 10 - 4), antigen processing and presentation of peptide antigen (FDR = 2.33 × 10 - 3) and eukaryotic translation initiation factor 4F complex (FDR = 2.52 × 10 - 2). CONCLUSION This study reported several RA-associated gene modules and their functional association networks.Cite this article: X. Xiao, J. Hao, Y. Wen, W. Wang, X. Guo, F. Zhang. Genome-wide association studies and gene expression profiles of rheumatoid arthritis: an analysis. Bone Joint Res 2016;5:314-319. DOI: 10.1302/2046-3758.57.2000502.
منابع مشابه
Molecular Detection of Bacterial Etiology of Rheumatoid Arthritis
Background and purpose: Etiology of rheumatoid arthritis is not fully recognized. The purpose of this study was to use universal and specific primers to trace bacteria in the blood and synovial fluid in patients with rheumatoid arthritis. Materials and methods: In this experimental study, a PCR method was developed to identify a wide range of bacteria in general and Staphylococcus aureus in sp...
متن کاملInvestigation of the plasma levels of CCL-17 and CCL-25 and their receptor gene expression in rheumatoid arthritis patients
Background and Aim: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease of unknown etiology. The chemokines and their related receptors have a pivotal role in migration and homing of leukocyte involved in the pathogenesis of RA. The goal of this study was to measure the plasma levels of CCL-17 and CCL-25 and their receptors gene (CCR4 and CCR9) expression in rheumatoid arthritis pa...
متن کاملStudying the Association between STAT4 Gene Polymorphism and Susceptibility to Rheumatoid Arthritis Disease: An Updated Meta-Analysis
متن کامل
Identification of gene-gene interaction using principal components
After more than 200 genome-wide association studies, there have been some successful identifications of a single novel locus. Thus, the identification of single-nucleotide polymorphisms (SNP) with interaction effects is of interest. Using the Genetic Analysis Workshop 16 data from the North American Rheumatoid Arthritis Consortium, we propose an approach to screen for SNP-SNP interaction using ...
متن کاملDifferential Expression of Rheumatoid Factor-Associated Cross-Reactive Idiotypes in Iranian Seropositive and Seronegative Patients with Rheumatoid Arthritis
High levels of rheumatoid factors (RF) are detectable in serum of the majority of patients with rheumatoid arthritis (RA), but 5-10% of patients remain seronegative (SN). Despite clinical and genetic similarities between these two subsets of RA, it has been proposed that they may be regarded as distinct clinical entities. Methods: In the present study a panel of monoclonal antibodies (mAb) rec...
متن کامل