title: Association of a common interferon regulatory factor 5 (IRF5) variant with increased risk of systemic lupus erythematosus (SLE).
abstract: Interferon regulatory factor 5 (IRF5) belongs to a family of transcription factors that control the transactivation of type I interferon system-related genes, as well as the expression of several other genes involved in immune response, cell signalling, cell cycle control and apoptosis. Two recent studies reported a significant association between the IRF5/rs2004640 T allele and systemic lupus erythematosus (SLE). The purpose of this study was to determine whether the reported rs2004640 T allele association could be replicated in our independent SLE case-control sample. We genotyped DNA samples from 370 white SLE-affected female subjects and 462 white healthy female controls using the TaqMan Assay-on-Demand for rs2004640, and performed a case-control genetic association analysis. Frequency of the rs2004640 T allele was significantly higher in cases than in controls (56.5% vs. 50%; P= 0.008). The odds ratio for T allele carriers was 1.68 (95% CI: 1.20 - 2.34; P= 0.003). Our results in an independent case-control sample confirm the robust association of the IRF5/rs2004640 T allele with SLE risk, and further support the relevance of the type I interferon system in the pathogenesis of SLE and autoimmunity.
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: F Y K
authors.initials: FY
authors.lastname: Demirci
authors.forename: S
authors.initials: S
authors.lastname: Manzi
authors.forename: R
authors.initials: R
authors.lastname: Ramsey-Goldman
authors.forename: R L
authors.initials: RL
authors.lastname: Minster
authors.forename: M
authors.initials: M
authors.lastname: Kenney
authors.forename: P S
authors.initials: PS
authors.lastname: Shaw
authors.forename: C M
authors.initials: CM
authors.lastname: Dunlop-Thomas
authors.forename: A H
authors.initials: AH
authors.lastname: Kao
authors.forename: E
authors.initials: E
authors.lastname: Rhew
authors.forename: F
authors.initials: F
authors.lastname: Bontempo
authors.forename: C
authors.initials: C
authors.lastname: Kammerer
authors.forename: M I
authors.initials: MI
authors.lastname: Kamboh
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D017398:Alternative Splicing; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors