Association of the autoimmunity locus 4q27 with juvenile idiopathic arthritis

Albers, H M; Kurreeman, Fina; Stoeken-Rijsbergen, Gerrie; Brinkman, Dmc; Kamphuis, S. S. M.; Rossum, Marion A J van; Girschick, H. J.; Wouters, Carine; Saurenmann, RK; Hoppenreijs, Esther P A H; Slagboom, P. Eline; Houwing-Duistermaat, Jeanine J.; Verduijn, Willem; Huizinga, T.W.J.; Cate, Rebecca ten; Toes, René E. M.; Schilham, MW

doi:10.1002/art.24296

Cited by 45 publications

(36 citation statements)

References 13 publications

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“…This association confirms a recently published association of the IL2_IL2 region with JIA susceptibility. 21 We performed a meta-analysis of the two studies, which yielded highly significant evidence for association (odds ratio 0.77 95% confidence interval 0.69-0.87, P ¼ 1 Â 10 À5 ) with no evidence for heterogeneity between the two cohorts (P ¼ 0.81). This finding is interesting in light of the previous confirmed association of the IL2RA gene with JIA 6 and may suggest that the IL2 pathway is particularly important in JIA susceptibility.…”

Section: Resultsmentioning

confidence: 99%

Association of the AFF3 gene and IL2/IL21 gene region with juvenile idiopathic arthritis

Hinks

Eyre

et al. 2010

Genes Immun

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Recent genetic studies have led to identification of numerous loci that are associated with susceptibility to autoimmune diseases. The strategy of using information from these studies has facilitated the identification of novel juvenile idiopathic arthritis (JIA) susceptibility loci, specifically, PTPN22 and IL2RA. Several novel autoimmune susceptibility loci have recently been identified, and we hypothesise that single-nucleotide polymorphisms (SNPs) within these genes may also be JIA susceptibility loci. Five SNPs within the genes AFF3, IL2/IL21, IL7R, CTLA4 and CD226, previously associated with multiple autoimmune diseases were genotyped, in a large data set of Caucasian JIA patients and controls, and tested for association with JIA. We identified two susceptibility loci for JIA, AFF3 and the IL2/IL21 region and additional weak evidence supporting an association with the CTLA4 and IL7R genes, which warrant further investigation. All results require validation in independent JIA data sets. Further characterisation of the specific causal variants will be required before functional studies can be performed.

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Section: Resultsmentioning

confidence: 99%

Association of the AFF3 gene and IL2/IL21 gene region with juvenile idiopathic arthritis

Hinks

Eyre

et al. 2010

Genes Immun

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“…IL-2/IL-21 rs6822844 showed a clear trend toward association with RA [65] . The KIAA1109-TENR-IL2-IL21 region has been associated with a wide variety of autoimmune diseases like type 1 diabetes (T1D) [66] , ulcerative colitis [67] , Crohn's disease [68] , celiac disease, Graves' disease (GD) [66] , systemic lupus erythematosus (SLE) [69] , psoriatic arthritis [70] , and juvenile idiopathic arthritis [71] . The rs6822844 within the KIAA1109-TENR-IL2-IL21 gene cluster has been linked to RA.…”

Section: The Il-2 Familymentioning

confidence: 99%

Interleukins and interleukin receptors in rheumatoid arthritis: Research, diagnostics and clinical implications

Magyari

Várszegi

Kövesdi

et al. 2014

WJO

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Rheumatoid arthritis (RA) is an autoimmune disease, resulting in a chronic, systemic inflammatory disorder. It may affect many tissues and organs, but it primarily affects the flexible joints. In clinical practice patient care generates many questions about diagnosis, prognosis, and treatment. It is challenging for health care specialists to keep up to date with the medical literature. This review summarizes the pathogenesis, the polymorphisms of interleukin and interleukin genes and the standard available and possible future immunologic targets for RA treatment. The identification of diseaseassociated interleukin and interleukin receptor genes can provide precious insight into the genetic variations prior to disease onset in order to identify the pathways important for RA pathogenesis. The knowledge of the complex genetic background may prove useful for developing novel therapies and making personalized medicine based on the individual's genetics.

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“…Especially rs6822844 has been extensively studied. It has been associated with celiac disease [12], UC [8,9,10,11], rheumatoid arthritis [14,16], type 1 diabetes [14], psoriatic arthritis [18], juvenile idiopathic arthritis [19,20], systemic lupus erythematosus [17] and Sjögren’s syndrome [17]. …”

Section: Discussionmentioning

confidence: 99%

“…The association of the IL2/IL21 region on chromosome 4q27 with celiac disease [12], type 1 diabetes [13,14,15], rheumatoid arthritis [14,16,17], psoriatic arthritis [18], juvenile idiopathic arthritis [19,20], systemic lupus erythematosus [17,21], Sjögren’s syndrome [17] and Grave’s disease [15] suggests this region as a general autoimmune risk locus and makes it also an interesting candidate locus for PBC. The frequency of classic autoimmune diseases is increased in both PSC patients and PBC patients and their first-degree relatives [22,23].…”

Section: Introductionmentioning

confidence: 99%

Analysis of IL2/IL21 Gene Variants in Cholestatic Liver Diseases Reveals an Association with Primary Sclerosing Cholangitis

Stallhofer¹,

Denk²,

Glas

et al. 2011

Digestion

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Background/Aims: The chromosome 4q27 region harboring IL2 and IL21 is an established risk locus for ulcerative colitis (UC) and various other autoimmune diseases. Considering the strong coincidence of primary sclerosing cholangitis (PSC) with UC and the increased frequency of other autoimmune disorders in patients with primary biliary cirrhosis (PBC), we investigated whether genetic variation in the IL2/IL21 region may also modulate the susceptibility to these two rare cholestatic liver diseases. Methods: Four strongly UC-associated single nucleotide polymorphisms (SNPs) within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block were genotyped in 124 PBC and 41 PSC patients. Control allele frequencies from 1,487 healthy, unrelated Caucasians were available from a previous UC association study. Results: The minor alleles of all four markers were associated with a decreased susceptibility to PSC (rs13151961: p = 0.013, odds ratio (OR) 0.34; rs13119723: p = 0.023, OR 0.40; rs6822844: p = 0.031, OR 0.41; rs6840978: p = 0.043, OR 0.46). Moreover, a haplotype consisting of the four minor alleles also had a protective effect on PSC susceptibility (p = 0.0084, OR 0.28). A haplotype of the four major alleles was independently associated with PSC when excluding the patients with concomitant inflammatory bowel disease (p = 0.033, OR 4.18). Conclusion: The IL2/IL21 region may be one of the highly suggestive but so far rarely identified shared susceptibility loci for PSC and UC.

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Association of the autoimmunity locus 4q27 with juvenile idiopathic arthritis

Cited by 45 publications

References 13 publications

Association of the AFF3 gene and IL2/IL21 gene region with juvenile idiopathic arthritis

Association of the AFF3 gene and IL2/IL21 gene region with juvenile idiopathic arthritis

Interleukins and interleukin receptors in rheumatoid arthritis: Research, diagnostics and clinical implications

Analysis of IL2/IL21 Gene Variants in Cholestatic Liver Diseases Reveals an Association with Primary Sclerosing Cholangitis

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