Dataset Information

FCGR2B and FCRLB gene polymorphisms associated with IgA nephropathy.

ABSTRACT:

Background

IgA nephropathy (IgAN) is a complex syndrome characterized by deposition of IgA and IgA containing immune complexes (ICs) composed of IgG and complement C3 proteins in the mesangial area of glomeruli. The low-affinity receptors for the Fc region of IgG (Fc?Rs) are involved in autoantibody/immune complex-induced organ injury as well as ICs clearance. The aim of the study was to associate multiple polymorphisms within FCGR gene locus with IgAN in a large Chinese cohort.

Patients and methods

60 single nucleotide polymorphisms (SNPs) spanning a 400 kb range within FCGR gene locus were analyzed in 2100 DNA samples from patients with biopsy proven IgAN and healthy age- and sex-matched controls from the same population in Chinese.

Results

Among the 60 SNPs investigated, 15 gene polymorphisms within FCGR gene locus (25%) were associated with susceptibility to IgAN. The most significantly associated SNPs within individual genes were FCGR2B rs12118043 (p?=?8.74*10(-3), OR 0.76, 95% CI 0.62-0.93), and FCRLB rs4657093 (p?=?2.28*10(-3), OR 0.77, 95% CI 0.65-0.91). Both conditional analysis and linkage disequilibrium analysis suggested they were independent signals associated with IgAN. Associations between FCGR2B rs12118043 and proteinuria (p?=?3.65×10(-2)) as well as gross hematuria (p?=?4.53×10(-2)), between FCRLB rs4657093 and levels of serum creatinine (p?=?2.67×10(-2)) as well as eGFR (p?=?5.41*10(-3)) were also observed. Electronic cis-expression quantative trait loci analysis supported their possible functional significance, with protective genotypes correlating lower gene expressions.

Conclusion

Our data from genetic associations and expression associations revealed potentially pathogenic roles of Fc receptor gene polymorphisms in IgAN.

SUBMITTER: Zhou XJ

PROVIDER: S-EPMC3625155 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

FCGR2B and FCRLB gene polymorphisms associated with IgA nephropathy.

Zhou Xu-jie XJ Cheng Fa-juan FJ Qi Yuan-yuan YY Zhao Yan-feng YF Hou Ping P Zhu Li L Lv Ji-cheng JC Zhang Hong H

PloS one 20130412 4

<h4>Background</h4>IgA nephropathy (IgAN) is a complex syndrome characterized by deposition of IgA and IgA containing immune complexes (ICs) composed of IgG and complement C3 proteins in the mesangial area of glomeruli. The low-affinity receptors for the Fc region of IgG (FcγRs) are involved in autoantibody/immune complex-induced organ injury as well as ICs clearance. The aim of the study was to associate multiple polymorphisms within FCGR gene locus with IgAN in a large Chinese cohort.<h4>Patie ...[more]

PMID: 23593433

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Project description:BackgroundImmunoglobulin A nephropathy (IgAN) is the most common primary glomerulopathy worldwide. However, the molecular events underlying IgAN remain to be fully elucidated. This study aimed to identify novel biomarkers of IgAN through bioinformatics analysis and elucidate the possible molecular mechanism.MethodsBased on the microarray datasets GSE93798 and GSE37460 downloaded from the Gene Expression Omnibus database, the differentially expressed genes (DEGs) between IgAN samples and normal controls were identified. Using the DEGs, we further performed a series of functional enrichment analyses. Protein-protein interaction (PPI) networks of the DEGs were constructed using the STRING online search tool and were visualized using Cytoscape. Next, hub genes were identified and the most important module among the DEGs, Biological Networks Gene Ontology tool (BiNGO), was used to elucidate the molecular mechanism of IgAN.ResultsIn total, 148 DEGs were identified, comprising 53 upregulated genes and 95 downregulated genes. Gene Ontology (GO) analysis indicated that the DEGs for IgAN were mainly enriched in extracellular exosome, region and space, fibroblast growth factor stimulus, inflammatory response, and innate immunity. Module analysis showed that genes in the top 1 significant module of the PPI network were mainly associated with innate immune response, integrin-mediated signaling pathway and inflammatory response. The top 10 hub genes were constructed in the PPI network, which could well distinguish the IgAN and control group in monocyte and tissue samples. We finally identified the integrin subunit beta 2 (ITGB2) and Fc fragment of IgE receptor Ig (FCER1G) genes that may play important roles in the development of IgAN.ConclusionsWe identified key genes along with the pathways that were most closely related to IgAN initiation and progression. Our results provide a more detailed molecular mechanism for the development of IgAN and novel candidate gene targets of IgAN.

Dataset Information

FCGR2B and FCRLB gene polymorphisms associated with IgA nephropathy.

Background

Patients and methods

Results

Conclusion

Publications

FCGR2B and FCRLB gene polymorphisms associated with IgA nephropathy.

Similar Datasets

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