{{Rsnum
|rsid=2004640
|Gene=IRF5
|Chromosome=7
|position=128938247
|Orientation=plus
|GMAF=0.404
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(G;G)
|geno2=(G;T)
|geno3=(T;T)
|Gene_s=IRF5
}}[[rs2004640]], a SNP in the [[IRF5]] gene in chromosomal region 7q32.1, is one of several SNPs associated with systemic [[lupus]] erythematosus (SLE). This association has been observed in multiple populations (Caucasian, Asian, and African-Americans).

The association was first noted in two relatively large studies of Caucasian patients.[PMID 15657875, PMID 16642019]

In ~600 Korean [[SLE]] patients, the odds ratio for the [[rs2004640]](T) risk allele was 1.44 (CI: 1.34-1.55, overall p=1.85x10e-23). The [[rs2004640]]-T/[[rs2280714]]-T haplotype involved in both the alternative splice donor site and the elevated expression of the [[IRF5]] protein also had a highly significant association with SLE (pooled p=2.11x 10e-16).{{PMID|17389033|OA=1
}}

{{PMID|18288123}} Reconfirmed for African-Americans

{{PMID|17166181}} Reconfirmed in ~370 female Caucasian patients

{{PMID|17189288|OA=1
}} Reconfirmed in ~380 UK [[SLE]] families

{{PMID|18311811}} Pooled data from two populations (Japanese and Korean) were combined to determine that the [[rs2004640]](T) allele frequency was significantly increased in [[SLE]] patients (p = 8.3 x 10<sup>-5</sup>).

{{PMID|18063667}} A variant located 64 bp upstream of the first untranslated exon (exon 1A), consisting of a 5 bp insertion/deletion CGGGG (rs77571059), may be the causative SNP in this region that is most responsible for increasing SLE risk.

{{PMID|18843785}} In a Korean population, [[rs2004640]] was associated with both the anti-CCP Ab-positive (odds ratio 1.47, CI: 1.15-1.88, pcorr = 0.01) and SE-positive group (odds ratio 1.54, CI: 1.14-2.09, pcorr = 0.03) forms of [[rheumatoid arthritis]].  Combined analysis pooling 3 independent cohorts yielded an association with an odds ratio of 1.21, CI: 1.07-1.38, pooled p = 0.0031 in a dominant model.

{{PMID|19116937}} rs2004640(T;T) is associated with susceptibility to systemic [[sclerosis]] in a study of ~800 French Caucasian patients, with an odds ratio of 1.58 (CI: 1.18 - 2.11, p trend 0.002).

{{PMID|19228650}} A meta-analysis comprising 5 case-control studies, totaling 6,582 [[rheumatoid arthritis]] cases and 5,375 controls, concluded that several [[IRF5]] gene SNPs were indeed (still) significantly associated with the disease. The [[rs2004640]](G) allele was associated with a slight protective effect (odds ratio 0.9, CI: 0.85-0.96, p = 0.002).

{{PMID|19479858}} Of 3 [[IRF5]] SNPs studied, the [[rs2280714]](A) SNP (and not this one) had the strongest association (odds ratio 1.42, CI: 1.15-1.75) in Japanese [[SLE]] patients.

{{PMID|18285424|OA=1
}} Association with multiple sclerosis (along with several other SNPs) was observed after combining data from Swedish and Spanish case/control studies and a Finnish trio study.

{{ neighbor
| rsid = 6953165
| distance = 91
}}
{{ neighbor
| rsid = 41298401
| distance = 6
}}

{{omim
|desc=SYSTEMIC LUPUS ERYTHEMATOSUS, SUSCEPTIBILITY TO, 10; SLEB10
|id=612251
|rsnum=2004640
}}

{{omim
|desc=RHEUMATOID ARTHRITIS; RA
|id=180300
|rsnum=2004640
}}

{{omim
|id=607218
|desc=INTERFERON REGULATORY FACTOR 5; IRF5
|rsnum=2004640
}}
{{PMID Auto
|PMID=19644887
|Title=STAT4 is a genetic risk factor for systemic sclerosis having additive effects with IRF5 on disease susceptibility and related pulmonary fibrosis
}}
{{PMID Auto
|PMID=19644876
|Title=Association of STAT4 and BLK, but not BANK1 or IRF5, with primary antiphospholipid syndrome
}}

{{PharmGKB
|RSID=rs2004640
|Name_s=
|Gene_s=IRF5
|Feature=
|Evidence=PubMed ID:16642019
|Annotation=A study at four independent case-control cohorts found an association of this SNP in the IRF5 gene with Systemic lupus erythematosus.
|Drugs=
|Drug Classes=
|Diseases=Lupus Erythematosus, Systemic
|Curation Level=Curated
|PharmGKB Accession ID=PA161889386
}}
{{PMID Auto
|PMID=19877059
|Title=BANK1 is a genetic risk factor for diffuse cutaneous systemic sclerosis and has additive effects with IRF5 and STAT4
}}

{{PMID Auto
|PMID=20980283
|Title=The interferon regulatory factor 5 gene confers susceptibility to rheumatoid arthritis and influences its erosive phenotype
}}
{{PMID Auto
|PMID=21239750
|Title=Association of IRF5 Polymorphisms with Susceptibility to Macrophage Activation Syndrome in Patients with Juvenile Idiopathic Arthritis
}}

{{omim
|id=607218
|rsnum=2004640
|variant=0002
}}

{{PMID Auto
|PMID=21471993
|Title=Interferon regulatory factor 5 gene variants and pharmacological and clinical outcome of Interferon? therapy in multiple sclerosis
}}

{{PMID Auto
|PMID=22544929
|Title=IRF5 Risk Polymorphisms Contribute to Interindividual Variance in Pattern Recognition Receptor-Mediated Cytokine Secretion in Human Monocyte-Derived Cells.
|OA=1
}}
{{PMID Auto
|PMID=17133578
|Title=Analysis of IRF5 gene functional polymorphisms in rheumatoid arthritis.
}}

{{PMID Auto
|PMID=17158136
|Title=IRF5 rs2004640-T allele, the new genetic factor for systemic lupus erythematosus, is not associated with rheumatoid arthritis.
|OA=1
}}

{{PMID Auto
|PMID=17393452
|Title=Structural insertion/deletion variation in IRF5 is associated with a risk haplotype and defines the precise IRF5 isoforms expressed in systemic lupus erythematosus.
}}

{{PMID Auto
|PMID=17412832
|Title=Three functional variants of IFN regulatory factor 5 (IRF5) define risk and protective haplotypes for human lupus.
|OA=1
}}

{{PMID Auto
|PMID=17615072
|Title=The ITGAV rs3738919-C allele is associated with rheumatoid arthritis in the European Caucasian population: a family-based study.
|OA=1
}}

{{PMID Auto
|PMID=17940599
|Title=Assembly of inflammation-related genes for pathway-focused genetic analysis.
|OA=1
}}

{{PMID Auto
|PMID=18045485
|Title=The candidate genes TAF5L, TCF7, PDCD1, IL6 and ICAM1 cannot be excluded from having effects in type 1 diabetes.
|OA=1
}}

{{PMID Auto
|PMID=18050197
|Title=Association of an IRF5 gene functional polymorphism with Sjogren's syndrome.
|OA=1
}}

{{PMID Auto
|PMID=18200047
|Title=IFN-regulatory factor 5 gene variants interact with the class I MHC locus in the Swedish psoriasis population.
}}

{{PMID Auto
|PMID=18438842
|Title=Association of interferon regulatory factor 5 haplotypes, similar to that found in systemic lupus erythematosus, in a large subgroup of patients with rheumatoid arthritis.
}}

{{PMID Auto
|PMID=18668568
|Title=Association of the IRF5 risk haplotype with high serum interferon-alpha activity in systemic lupus erythematosus patients.
|OA=1
}}

{{PMID Auto
|PMID=18752149
|Title=Association of IRF5 gene polymorphisms with rheumatoid arthritis in a Tunisian population.
}}

{{PMID Auto
|PMID=19043711
|Title=Association between the rs2004640 functional polymorphism of interferon regulatory factor 5 and systemic lupus erythematosus: a meta-analysis.
}}

{{PMID Auto
|PMID=19109131
|Title=Cutting edge: autoimmune disease risk variant of STAT4 confers increased sensitivity to IFN-alpha in lupus patients in vivo.
|OA=1
}}

{{PMID Auto
|PMID=19302705
|Title=Testing for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in a European family-based study.
|OA=1
}}

{{PMID Auto
|PMID=19591781
|Title=The search for lupus biomarkers.
|OA=1
}}

{{PMID Auto
|PMID=19778912
|Title=Association of TNFSF4 (OX40L) polymorphisms with susceptibility to systemic sclerosis.
|OA=1
}}

{{PMID Auto
|PMID=19849816
|Title=Genetics of rheumatic disease.
|OA=1
}}

{{PMID Auto
|PMID=19918036
|Title=Lack of association between IRF5 gene polymorphisms and biopsy-proven giant cell arteritis.
}}

{{PMID Auto
|PMID=19918037
|Title=Association of interleukin 23 receptor polymorphisms with anti-topoisomerase-I positivity and pulmonary hypertension in systemic sclerosis.
|OA=1
}}

{{PMID Auto
|PMID=19923204
|Title=Genetic background of systemic sclerosis: autoimmune genes take centre stage.
}}

{{PMID Auto
|PMID=20080916
|Title=Promoter insertion/deletion in the IRF5 gene is highly associated with susceptibility to systemic lupus erythematosus in distinct populations, but exerts a modest effect on gene expression in peripheral blood mononuclear cells.
}}

{{PMID Auto
|PMID=20112383
|Title=Genetic variants and disease-associated factors contribute to enhanced interferon regulatory factor 5 expression in blood cells of patients with systemic lupus erythematosus.
|OA=1
}}

{{PMID Auto
|PMID=20137629
|Title=[Relationship between polymorphism sites of IRF5, TLR-9 and SLE patients in Shandong Han population].
}}

{{PMID Auto
|PMID=20231204
|Title=Phenotype-haplotype correlation of IRF5 in systemic sclerosis: role of 2 haplotypes in disease severity.
}}

{{PMID Auto
|PMID=20383147
|Title=Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus.
|OA=1
}}

{{PMID Auto
|PMID=20439292
|Title=Genetic variants in the prediction of rheumatoid arthritis.
}}

{{PMID Auto
|PMID=20479942
|Title=Genetic risk factors in lupus nephritis and IgA nephropathy--no support of an overlap.
|OA=1
}}

{{PMID Auto
|PMID=20639879
|Title=Variants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis.
|OA=1
}}

{{PMID Auto
|PMID=20652065
|Title=Interferon alpha in systemic lupus erythematosus.
|OA=1
}}

{{PMID Auto
|PMID=21149496
|Title=NLRP1 influences the systemic sclerosis phenotype: a new clue for the contribution of innate immunity in systemic sclerosis-related fibrosing alveolitis pathogenesis.
}}

{{PMID Auto
|PMID=21834935
|Title=A meta-analysis of the association of IRF5 polymorphism with systemic lupus erythematosus.
}}

{{PMID Auto
|PMID=21898142
|Title=Association of IRF5 polymorphisms with susceptibility to hemophagocytic lymphohistiocytosis in children.
}}

{{PMID Auto
|PMID=22179739
|Title=Interferon regulatory factor 5 gene polymorphism confers risk to several rheumatic diseases and correlates with expression of alternative thymic transcripts.
}}

{{PMID Auto
|PMID=23073787
|Title=Associations between interferon regulatory factor 5 polymorphisms and rheumatoid arthritis: a meta-analysis
}}
{{GET Evidence
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs2004640
|overall_frequency_n=38
|overall_frequency_d=86
|overall_frequency=0.44186
|n_genomes=21
|n_genomes_annotated=0
|n_haplomes=28
|n_articles=1
|n_articles_annotated=0
|in_pharmgkb=Y
|autoscore=1
|webscore=N
}}

{{PMID Auto
|PMID=23372721
|Title=The Systemic Lupus Erythematosus IRF5 Risk Haplotype Is Associated with Systemic Sclerosis
|OA=1
}}

{{PMID Auto
|PMID=23392701
|Title=Association of rs10954213 polymorphisms and haplotype diversity in interferon regulatory factor 5 with systemic lupus erythematosus: A meta-analysis
}}

{{PMID Auto
|PMID=23801380
|Title=Association of the IRF5 rs2004640 polymorphism with rheumatoid arthritis: a meta-analysis
}}

{{PMID Auto
|PMID=24350899
|Title=Molecular Effects of Autoimmune-Risk Promoter Polymorphisms on Expression, Exon Choice, and Translational Efficiency of Interferon Regulatory Factor 5
}}

{{PMID Auto
|PMID=23288367
|Title=Interferon regulatory factor 5 polymorphisms in sarcoidosis.
}}

{{PMID Auto
|PMID=25036352
|Title=Association between IRF5 polymorphisms and autoimmune diseases: a meta-analysis
}}

{{PMID Auto
|PMID=24116155
|Title=Two functional variants of IRF5 influence the development of macular edema in patients with non-anterior uveitis
}}
{{on chip | 23andMe v2}}