rs6822844

This case-control study analyzes 28 SNPs in 26 inflammatory response genes in 343 patients (100 with appendicitis, 243 controls) using TaqMan genotyping. Significant associations were found for IL-13 rs1800925 (OR=6.02, 95% CI 1.52-23.78), IL-17 rs2275913 (OR=2.38, 95% CI 1.24-4.57), and CCL22 rs223888 (OR=0.12, 95% CI 0.02-0.90), suggesting a genetic-driven inflammatory response as a pathogenic mechanism in appendicitis.

This Bayesian hierarchical meta-analysis of 37 case-control studies (23,506 RA patients, 25,984 controls) examined genetic polymorphisms in the IL23R, IL21, and IL17A genes for association with rheumatoid arthritis (RA) risk. The IL23R rs1343151 minor A allele significantly increased RA risk (Log OR = 0.085, 95% CI = 0.008–0.156), while the IL23R rs2201841 C allele significantly decreased RA risk (Log OR = −0.544, 95% CI = −1.0–−0.065). The analysis found no significant associations between IL21 rs6822844 or IL17A rs2275913 polymorphisms and RA susceptibility, suggesting that genetic variations in IL23R, but not IL21 or IL17A, are involved in RA pathogenesis.

This meta-analysis of 22,233 CAD cases and 64,762 controls tested 41 celiac disease-associated SNPs for association with coronary artery disease (CAD). While 58.5% of celiac disease risk alleles showed positive association with CAD (OR 1.001-1.081), this was not significantly different from the 50% expected by chance (p=0.069). Only rs653178 at the SH2B3/ATXN2 locus achieved study-wide statistical significance (OR 1.081, p=2.2×10⁻⁶), likely through pleiotropic effects. The findings provide no convincing evidence that genetic variants associated with celiac disease contribute to CAD risk.

This extended UK genome-wide association study identified a novel rheumatoid arthritis susceptibility locus at 22q12 (rs1043099, P = 6.9 × 10⁻⁹, OR = 0.84) in 3,034 cases and 5,271 controls, and confirmed 16 previously known RA loci, strengthening evidence for genetic contributors to RA in the UK population.

This systematic literature review examines interleukin and interleukin receptor gene polymorphisms associated with rheumatoid arthritis (RA) pathogenesis, diagnostics, and treatment. The paper summarizes polymorphisms in multiple IL genes (IL-1B rs16944, rs1143634; IL-6 rs1800795, rs1800796; IL-10 rs1800896; IL-23R rs11209026; IL-17A rs2275913 and others) across diverse populations, their associations with RA susceptibility and disease severity, and discusses current and future immunologic therapeutic targets including TNF inhibitors and IL-6 receptor antagonists.

This study fine-maps the IL2/IL21 genetic association with systemic lupus erythematosus (SLE) in two large independent sample sets: European-derived (4,248 lupus patients, 3,818 controls) and African-American (1,569 patients, 1,893 controls). Using conditional analysis and trans-ethnic mapping, the researchers localized the primary genetic effect to two SNPs in high linkage disequilibrium: rs907715 within IL21 (OR=1.16, 95% CI 1.10-1.22, P=2.17×10⁻⁸) and rs6835457 in the 3'-UTR flanking region of IL21 (OR=1.11, 95% CI 1.05-1.17, P=9.35×10⁻⁵). The findings establish genome-wide significance for the IL2/IL21 locus in lupus genetic susceptibility.

This haplotype-based case-control study in 245 Han Chinese ulcerative colitis (UC) patients and 300 controls examined six known UC susceptibility loci. The authors identified IL2 SNP rs2069762 (P=7.0×10⁻⁴, OR=1.54, 95% CI 1.20-1.99) and IL21 SNP rs2055979 (P=1.2×10⁻⁴, OR=1.50, 95% CI 1.17-1.92) as independently associated with UC, demonstrating that unlike in Caucasians, IL2 and IL21 occupy separate linkage disequilibrium blocks in Han Chinese populations. They also identified rs17375018 in IL23R associated with disease extent (pancolitis; P=0.002, OR=2.38, 95% CI 1.41-4.02).

This cohort study of 2,324 subjects with inflammatory polyarthritis tested 17 rheumatoid arthritis (RA) susceptibility SNPs for association with all-cause and cardiovascular disease (CVD) mortality. Carriage of the CCL21 risk allele rs2812378 was associated with increased CVD mortality (HR 1.33, 95% CI 1.01-1.75) and all-cause mortality (HR 1.40, 95% CI 1.04-1.87), with the strongest effects observed in anti-CCP antibody-positive patients with both the CCL21 risk alleles and shared epitope (SE) alleles (all-cause HR 3.20, 95% CI 1.52-6.72; CVD HR 3.73, 95% CI 1.30-10.72). SNPs at the TRAF1/C5 locus were not significantly associated with mortality in this study.

This study confirmed association between rs6822844 in the IL2-IL21 region and multiple autoimmune diseases in non-European populations, with significant associations in Colombian samples for systemic lupus erythematosus (OR 0.50, P=0.008), type 1 diabetes (OR 0.43, P=0.014), rheumatoid arthritis (OR 0.61, P=0.019), and primary Sjögren's syndrome (OR 0.46, P=0.033). Meta-analysis of 23 populations showed highly significant overall association (P=2.61×10⁻²⁵, OR 0.73) and disease-specific associations with inflammatory bowel disease (P=3.48×10⁻¹², OR 0.74), rheumatoid arthritis (P=3.61×10⁻⁶, OR 0.77), type 1 diabetes (P=5.33×10⁻⁵, OR 0.61), and celiac disease (P=5.30×10⁻³, OR 0.72).

This multi-cohort genetic association study of 1,283 RA patients found that the PTPRC/CD45 gene variant rs10919563 (G allele) is associated with favorable response to anti-TNF therapy (OR 0.55, P=0.0001). Of 31 established RA risk alleles tested, only PTPRC reached genome-wide significance for therapy response, with stronger associations in autoantibody-positive patients (OR 0.55, 95% CI 0.39-0.76) compared to seronegative patients.

This study examined 27 previously identified rheumatoid arthritis (RA) risk alleles in 556 autoantibody-positive African-American RA cases and 791 controls. Twenty-four of 27 SNPs showed consistent odds ratios between African-Americans and Europeans; three SNPs (CCR6 rs3093023, TAGAP rs394581, TNFAIP3 rs6920220) showed opposite directions of effect. A genetic risk score analysis indicated that African-American cases were significantly enriched for European RA risk alleles (p=0.00005), suggesting that RA genetic risk factors are largely shared across ancestry groups.

This association study of 664 German Wegener's granulomatosis (WG) patients and 952 controls evaluated 22 SNPs across 13 candidate genes identified from RA and SLE studies. The strongest finding was a protective four-SNP IRF5 haplotype (rs2004640_G/rs60344245_del/rs2070197_T/rs10954213_G) with reduced WG risk (p=0.0000897, OR 0.73, 95% CI 0.62-0.85). SNPs in TNFAIP3 and CDK6 also showed nominally significant associations, suggesting WG shares some genetic risk factors with other autoimmune diseases.

A case-control study of 1,123 Korean rheumatoid arthritis patients and 1,008 controls found that genetic variants at PTPN22, TRAF1/C5, 6q23, 4q27, CD40, and CCL21 previously associated with Caucasian RA were not associated with Korean RA. The PADI4 variant rs2240340 showed strong association (p=1.15×10⁻⁸, OR=1.43), demonstrating substantial genetic heterogeneity between ethnic populations.

This case-control association study examined the 4q27 locus (rs6822844) in 655 juvenile idiopathic arthritis (JIA) patients and 791 controls across two independent sample sets. The T allele showed a protective effect, with a combined allelic odds ratio of 0.76 (95% CI 0.62-0.93, P = 7.08 × 10−3), demonstrating significant association with JIA, particularly in polyarticular disease subtypes (extended oligoarthritis OR = 0.55, P = 0.019; RF-negative polyarthritis OR = 0.69, P = 0.038).

This systematic literature review examines interleukin (IL) and interleukin receptor gene polymorphisms associated with rheumatoid arthritis (RA), covering studies from the past 10 years. The review discusses the pathogenesis of RA as a multifactorial autoimmune disease where genetic factors account for approximately 60% of disease risk. Multiple polymorphisms across IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-15, IL-17, IL-18, and IL-23R genes have been investigated in various populations, with inconsistent results across populations. The paper also reviews current and future therapeutic targets including anti-TNF, anti-IL-1, anti-IL-6, and anti-IL-17 treatments.

A meta-analysis of 4,107 type 2 diabetes cases and 5,187 controls from three GWA studies found no evidence that common variants altering circulating inflammatory protein levels (IL-18, IL-6R, CRP, IL1RN, PAI1, MIF) or variants predisposing to autoimmune diseases (type 1 diabetes, rheumatoid arthritis, Crohn's disease, celiac disease, multiple sclerosis, SLE) are associated with type 2 diabetes risk. For example, rs2250417 in IL18 showed OR=1.00 (95% CI 0.99-1.03) versus the expected OR of ~1.15 if inflammation were causal, suggesting inflammatory markers are likely secondary rather than causative in type 2 diabetes.