rs7517847

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 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 investigated 34 SNPs in 18 Crohn's disease susceptibility genes in 62 pediatric CD patients and 46 controls with known Mycobacterium avium subspecies paratuberculosis (MAP) status. Mutations in TLR4 (rs4986790, Asp299Gly) and IL10RA (rs2229113, Gly330Arg) were significantly associated with MAP-positive CD (27.6% vs 6.1%, p=0.021 and 62.1% vs 33.3%, p=0.024, respectively), with a synergistic interaction (OR=7.39, 95% CI 2.25-24.27). Functional studies showed IL-10 and TNFα production were significantly lower in CD patients with NOD2 mutations, and IL10R and TLR4 receptor expression were elevated on NK cells and NK T cells harboring NOD2 mutations.

This case-control association study examined IL-23R gene polymorphisms in 75 Chinese Han ITP patients and 81 controls. IL-23R rs1884444 GT/TT variant genotypes showed significant association with increased ITP risk (OR 2.776, 95% CI 1.086-7.090, p=0.028), while three other SNPs (rs10889677, rs11209032, rs7517847) showed no significant associations. IL-23R polymorphisms were not associated with response to high-dose dexamethasone therapy.

This case-control association study examines IL23R gene variants in three autoimmune diseases. The authors genotyped 6 IL23R SNPs in 263 psoriasis, 199 Crohn's disease, 282 ulcerative colitis (UC) patients, and 253 controls. rs1884444 TT conferred risk for UC (OR=3.13, p=0.001) and psoriasis (OR=2.68, p=0.005), while rs7517847 GG was protective for CD (OR=0.48, p=0.017). Haplotype analysis revealed 8 distinct haplotypes; haplotype 5 was significantly elevated in UC (OR=2.50, p=0.003), while haplotypes 6 and 8 conferred risk for CD. The study demonstrates that haplotype analysis reveals disease-specific genetic effects not detected by single SNP analysis.

A meta-analysis of 10 studies (14 separate comparisons) examining IL-23R polymorphisms and ankylosing spondylitis (AS) susceptibility. The study found significant associations between rs11209032 (OR=1.182, 95% CI 1.120-1.249) and AS in the overall population, with stronger association in Europeans (OR=1.234) but not in Asians (OR=1.030). Similar patterns were observed for rs1004819, rs10489629, rs1343151, and rs1495965. rs11209026 and rs11465804 also showed significant protective effects in Europeans (OR=0.611 and OR=0.677, respectively).

Study of 354 African American Crohn's disease cases and 354 controls examined the contribution of European admixture and major established CD risk genes. Mean European ancestry was similar between cases (20.9%) and controls (20.4%, p=0.58). Significant associations were found with NOD2 carrier status (OR 3.28, p=0.007), ATG16L1 Thr300Ala (p=0.003), IBD5 locus genes SLC22A4 L503F (p=0.05) and SLC22A5 g-207c (p=0.03), and IL23R rs2201841 (p=0.03), but not IRGM variants.

A case-control study of 226 bladder cancer patients and 270 Chinese controls found that the IL23R gene polymorphism rs10889677 (A/C) was significantly associated with bladder cancer risk, with the C allele conferring increased susceptibility (OR 1.818, 95% CI 1.349-2.449). Two other IL23R variants (rs7517847 and rs11465817) showed no significant association. The findings suggest IL23R plays an important role in bladder cancer susceptibility in the Chinese population.

Meta-analysis of 18 case-control studies examining IL-23R polymorphisms and Crohn's disease (CD) susceptibility. Two polymorphisms showed significant protective associations: rs11209026 (Arg381Gln) with OR=0.43 (95% CI: 0.37-0.50, P<0.00001) and rs7517847 with OR=0.49 (95% CI: 0.38-0.64, P<0.00001 for G/G vs. T/T comparison). Other examined SNPs (rs1004819, rs10889677, rs1495965) showed no significant associations. Caucasian populations showed the strongest protective effects for Arg381Gln.

Genome-wide association study of 116 children with cardiac neonatal lupus (116 cases, 3,351 controls) identified 17 significant SNPs in the HLA region at 6p21, with the strongest association at rs3099844 (OR 3.34, P=4.52×10⁻¹⁰) near the MICB gene. Non-HLA associations were found at rs743446 (21q22, OR 2.40, P=5.45×10⁻⁶), rs2403106 (12q21, OR 2.48, P=2.62×10⁻⁶), rs1391511 (10p15, OR 1.84, P=6.6×10⁻⁶), and rs1890645 (1q31, OR 2.98, P=3.52×10⁻⁶). Results suggest genetic polymorphisms in inflammatory and apoptotic pathways contribute to cardiac injury in fetuses exposed to maternal anti-Ro/SSA antibodies.

This case-control study investigated the association between IL23R gene variants and systemic lupus erythematosus (SLE) in 383 Hungarian SLE patients and 253 healthy controls. Nine IL23R SNPs (rs11805303, rs10889677, rs1004819, rs2201841, rs11209032, rs11209026, rs10489629, rs7517847, rs7530511) were genotyped using PCR-RFLP methods. The study found no significant differences in genotype distributions, allele frequencies, or haplotypes between SLE patients and controls, suggesting that IL23R polymorphisms do not play a role in SLE susceptibility in the Hungarian population.

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.

This case-control study examined the association between 8 MYO9B SNPs and inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC) in 652 CD patients, 650 UC patients, and 1190 British controls. The strongest association was found with rs2305767 (OR 0.62, 95% CI 0.53-0.73, p=0.001 for CD), an intronic noncoding variant. A haplotype analysis identified the 11111111 haplotype as carrying increased risk (OR 1.87 for CD), though the study failed to confirm significant associations with UC.

This case-control association study examined seven IL23R gene polymorphisms in 1,204 Korean RA patients and 979 controls using TaqMan genotyping. No statistically significant associations were found between IL23R variants (rs1004819, rs7517847, rs10489629, rs2201841, rs1343151, rs11209032, rs1495965) and rheumatoid arthritis susceptibility after multiple testing correction, suggesting IL23R does not play a significant role in RA genetics in the Korean population.

This case-control study examined seven IL23R polymorphisms (rs1004819, rs7517847, rs10489629, rs2201841, rs1343151, rs11209032, rs1495965) in 602 Korean SLE patients and 991 healthy controls using TaqMan genotyping. None of the IL23R genetic variants differed significantly between SLE patients and controls in any genetic model (all p > 0.08), suggesting that IL23R polymorphisms play no role in SLE susceptibility in the Korean population, despite previous associations with inflammatory bowel disease in European populations.

Population-based case-control study (213 CD cases, 315 controls) examining associations between IBD5, IL23R, ATG16L1, and NOD2 genetic variants and Crohn's disease risk. IL23R rs10889677 showed the strongest association with CD (OR=2.47, 95% CI 1.70-3.57), while rs11209026 and rs7517848 were protective (OR=0.44 and OR=0.62 respectively). ATG16L1 Thr300Ala showed strong association (homozygote OR=2.38). Evidence suggested gene-gene interactions between IBD5 and IL23R loci.

This case-control study of 707 Spanish IBD patients (344 with Crohn's disease, 363 with ulcerative colitis) and 547 controls found significant associations between IL23R SNPs and IBD, with rs7517847 showing the strongest effect (OR = 0.79, p = 0.005). IL12B rs6887695 also showed association with IBD (OR = 1.24, p = 0.012), particularly in ulcerative colitis. No significant interaction between IL23R and IL12B polymorphisms was detected.

This case-control study examined the association of CARD15, IL23R, and ATG16L1 variants with Crohn's disease (CD) susceptibility in a Brazilian population of 187 CD patients and 255 controls. CARD15 variants R702W (OR=3.77) and 3020insC (OR=4.56) and IL23R variants rs1004819 (OR=1.46), rs11209026 (OR=0.36, protective), and rs10889677 (OR=1.38) showed significant associations with CD. However, no significant genotype-phenotype correlations were found for disease location, behavior, or severity in the Brazilian population.

PhD thesis describing comprehensive genome-wide association studies of acute anterior uveitis (AAU) in European (2,752 cases, 3,836 controls) and East Asian (821 cases, 4,898 controls) populations. European descent GWAS identified HLA-B at genome-wide significance plus 11 suggestive loci (ERAP1, NOS2, MERTK). East Asian GWAS identified HLA-B and ERAP1 at genome-wide significance plus 12 suggestive loci (GPR68, RHBDD2). Mendelian randomization confirmed ERAP1 as functionally relevant and showed genetically predicted CRP levels positively associated with AAU risk.

This case-control association study examined whether IL-12B and IL-23R polymorphisms associated with chronic inflammatory diseases also contribute to myocardial infarction (MI) risk in 738 British MI patients and 716 controls. Testing five variants (rs11209026, rs7517847, rs1343151, rs10889677 in IL-23R and rs3212227 in IL-12B) showed no significant associations with MI (all p > 0.05), suggesting these variants are unlikely to be major contributors to MI pathogenesis despite their strong protective effects in inflammatory bowel disease and psoriasis.

This replication study confirms IL23R as a susceptibility gene for Crohn's disease (CD) and ulcerative colitis (UC) in 604 CD and 647 UC UK patients with 1,149 controls. The nonsynonymous SNP rs11209026 (Arg381Gln) showed protective association with CD (P=6.65×10⁻⁶, OR=0.43), while rs7517847 was the strongest signal (P=4.9×10⁻⁹, OR=0.65). Three independent variants (rs7517847, rs11209026, rs1343151) contribute to CD susceptibility, with suggestive epistasis with the IBD5 haplotype but weaker effects in UC.

A candidate gene study of 837 psoriasis cases and 816 controls identified protective variants in IL-23 signaling genes. IL23R p.Arg381Gln (rs11209026) showed reduced frequency in cases vs controls (P=0.00014, OR=0.49). IL12B variants rs10045431 (P=0.0001, OR=1.41) and rs3212227 (P=0.036, OR=0.76) showed independent associations, establishing IL23 receptor signaling as a major pathway in psoriasis susceptibility.