Testing for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in a European family-based study

Teixeira, Vítor Hugo; Pierlot, Céline; Migliorini, Paola; Balsa, Alejandro; Westhovens, René; Barrera, Pilar; Alves, Helena; Vaz, Carlos; Fernandes, Margarida Sá; Pascual‐Salcedo, Dora; Bombardieri, Stefano; Dequeker, Jan; Radstake, Timothy R. D. J.; Riel, Piet van; Putte, Leo van de; Lopes-Vaz, Antonio; Bardin, Thomas; Prum, Bernard; Cornélis, François; Petit-Teixeira, Élisabeth

doi:10.1186/ar2654

Cited by 30 publications

(38 citation statements)

References 28 publications

(34 reference statements)

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“…In this sense, regions previously associated with CD were involved in other autoimmune diseases: IL18RAP in type 1 diabetes [10] or IL2-IL21 in ulcerative colitis [5] and rheumatoid arthritis [26]. On the other hand, genes originally involved in predisposition to other diseases have now been associated with CD risk, such as OLIG3/TNFAIP3, which was previously associated with rheumatoid arthritis and systemic lupus erythematosus [11] and the IBD susceptibility factor DLG5 [27].…”

Section: Discussionmentioning

confidence: 99%

Lack of association of NKX2-3, IRGM, and ATG16L1 inflammatory bowel disease susceptibility variants with celiac disease

et al. 2009

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Section: Discussionmentioning

confidence: 99%

Lack of association of NKX2-3, IRGM, and ATG16L1 inflammatory bowel disease susceptibility variants with celiac disease

et al. 2009

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“…There have been several studies testing this region for association with RA in European Caucasian sample sets, with varying levels of supporting evidence (0.24 > P > 2.8 × 10 -4 ) [6,12,20,21]. There is extensive linkage disequilibrium across the region, hampering fine-mapping efforts [13], however it is clear that there are two independent autoimmune associated regions within the KIAA1109-TENR-IL2-IL21 gene cluster.…”

Section: Introductionmentioning

confidence: 99%

Only one independent genetic association with rheumatoid arthritis within the KIAA1109-TENR-IL2-IL21 locus in Caucasian sample sets: confirmation of association of rs6822844 with rheumatoid arthritis at a genome-wide level of significance

et al. 2010

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IntroductionThe single nucleotide polymorphism (SNP) rs6822844 within the KIAA1109-TENR-IL2-IL21 gene cluster has been associated with rheumatoid arthritis (RA). Other variants within this cluster, including rs17388568 that is not in linkage disequilibrium (LD) with rs6822844, and rs907715 that is in moderate LD with rs6822844 and rs17388568, have been associated with a number of autoimmune phenotypes, including type 1 diabetes (T1D). Here we aimed to: one, confirm at a genome-wide level of significance association of rs6822844 with RA and, two, evaluate whether or not there were effects independent of rs6822844 on RA at the KIAA1109-TENR-IL2-IL21 locus.MethodsA total of 842 Australasian RA patients and 1,115 controls of European Caucasian ancestry were genotyped for rs6822844, rs17388568 and rs907715. Meta-analysis of these data with published and publicly-available data was conducted using STATA.ResultsNo statistically significant evidence for association was observed in the Australasian sample set for rs6822844 (odds ratio (OR) = 0.95 (0.80 to 1.12), P = 0.54), or rs17388568 (OR = 1.03 (0.90 to 1.19), P = 0.65) or rs907715 (OR = 0.98 (0.86 to 1.12), P = 0.69). When combined in a meta-analysis using data from a total of 9,772 cases and 10,909 controls there was a genome-wide level of significance supporting association of rs6822844 with RA (OR = 0.86 (0.82 to 0.91), P = 8.8 × 10-8, P = 2.1 × 10-8 including North American Rheumatoid Arthritis Consortium data). Meta-analysis of rs17388568, using a total of 6,585 cases and 7,528 controls, revealed no significant association with RA (OR = 1.03, (0.98 to 1.09); P = 0.22) and meta-analysis of rs907715 using a total of 2,689 cases and 4,045 controls revealed a trend towards association (OR = 0.93 (0.87 to 1.00), P = 0.07). However, this trend was not independent of the association at rs6822844.ConclusionsThe KIAA1109-TENR-IL2-IL21 gene cluster, that encodes an interleukin (IL-21) that plays an important role in Th17 cell biology, is the 20th locus for which there is a genome-wide (P ≤ 5 ×10-8) level of support for association with RA. As for most other autoimmune diseases, with the notable exception of T1D, rs6822844 is the dominant association in the locus. The KIAA1109-TENR-IL2-IL21 locus also confers susceptibility to other autoimmune phenotypes with a heterogeneous pattern of association.

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“…This locus has been associated with auto-inflammatory disorders such as celiac disease, 11,12 ulcerative colitis, 13,14 and rheumatoid arthritis. 15,16 Given the nature of GWAS studies, namely associations between a SNP and a phenotype, we can only postulate as to the potential role of this locus in the pathogenesis of acute vaso-occlusive pain, a complex phenomenon involving tissue ischemia, hypoxia-reperfusion injury, immune responses and inflammation, 17,18 and interactions between red blood cells, endothelium, and leukocytes regulated by regulated by T-cell cytokines and adhesion molecules. 19,20 Interleukin-2 (IL-2) and interleukin-21 (IL-21) may modulate acute pain in SCD through their effects on inflammation and immune responses.…”

Section: To the Editormentioning

confidence: 99%

Genome-wide association study to identify variants associated with acute severe vaso-occlusive pain in sickle cell anemia

Chaturvedi

Bhatnagar

Bean

et al. 2017

Blood

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Testing for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in a European family-based study

Cited by 30 publications

References 28 publications

Lack of association of NKX2-3, IRGM, and ATG16L1 inflammatory bowel disease susceptibility variants with celiac disease

Lack of association of NKX2-3, IRGM, and ATG16L1 inflammatory bowel disease susceptibility variants with celiac disease

Only one independent genetic association with rheumatoid arthritis within the KIAA1109-TENR-IL2-IL21 locus in Caucasian sample sets: confirmation of association of rs6822844 with rheumatoid arthritis at a genome-wide level of significance

Genome-wide association study to identify variants associated with acute severe vaso-occlusive pain in sickle cell anemia

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