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Effects of IRF5 lupus risk haplotype on pathways predicted to influence B cell functions.


ABSTRACT: Both genetic and environmental interactions affect systemic lupus erythematosus (SLE) development and pathogenesis. One known genetic factor associated with lupus is a haplotype of the interferon regulatory factor 5 (IRF5) gene. Analysis of global gene expression microarray data using gene set enrichment analysis identified multiple interferon- and inflammation-related gene sets significantly overrepresented in cells with the risk haplotype. Pathway analysis using expressed genes from the significant gene sets impacted by the IRF5 risk haplotype confirmed significant correlation with the interferon pathway, Toll-like receptor pathway, and the B-cell receptor pathway. SLE patients with the IRF5 risk haplotype have a heightened interferon signature, even in an unstimulated state (P = 0.011), while patients with the IRF5 protective haplotype have a B cell interferon signature similar to that of controls. These results identify multiple genes in functionally significant pathways which are affected by IRF5 genotype. They also establish the IRF5 risk haplotype as a key determinant of not only the interferon response, but also other B-cell pathways involved in SLE.

SUBMITTER: Guthridge JM 

PROVIDER: S-EPMC3304673 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Effects of IRF5 lupus risk haplotype on pathways predicted to influence B cell functions.

Guthridge Joel M JM   Clark Daniel N DN   Templeton Amanda A   Dominguez Nicolas N   Lu Rufei R   Vidal Gabriel S GS   Kelly Jennifer A JA   Kauffman Kenneth M KM   Harley John B JB   Gaffney Patrick M PM   James Judith A JA   Poole Brian D BD  

Journal of biomedicine & biotechnology 20120222


Both genetic and environmental interactions affect systemic lupus erythematosus (SLE) development and pathogenesis. One known genetic factor associated with lupus is a haplotype of the interferon regulatory factor 5 (IRF5) gene. Analysis of global gene expression microarray data using gene set enrichment analysis identified multiple interferon- and inflammation-related gene sets significantly overrepresented in cells with the risk haplotype. Pathway analysis using expressed genes from the signif  ...[more]

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