rs11209026

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 examined ankylosing spondylitis (AS) clinical features in 70 Orenburg region patients in relation to genetic and environmental factors. HLA-B27 was found in 92.86% of AS patients vs 5% of controls (OR=247.0, 95% CI 27.2–2245.0, p<0.001). Heterozygous genotypes at ERAP1 rs10050860 and rs17482078, combined with reduced zinc levels, were associated with functional impairment. IL23R rs11209026 heterozygous [G/A] genotype with chromium and nickel imbalance showed greatest impact on AS disease activity.

This association study compared genetic susceptibility loci frequencies between 312 familial and 190 sporadic ankylosing spondylitis (AS) cases. HLA-B27 was significantly more prevalent in familial cases (OR: 5.41, p=8.4×10⁻⁸), while non-MHC susceptibility variants in IL23R, IL1R2, ANTXR2, ERAP1, and intergenic regions on chromosomes 2p15 and 21q22 showed no significant differences between familial and sporadic cases.

This is a Turkish master's thesis investigating the relationship between the rs924080 variant in the IL23R-IL12RB2 intergenic region (previously identified as Behçet's disease-associated in GWAS studies, P<0.0001) and IL23R/IL12RB2 gene expression in healthy volunteers. The study examined 14 healthy subjects (6 heterozygous AG, 4 homozygous AA, 4 GG control for the risk A allele) and found that the rs924080 A risk allele significantly enhanced IL-23R stimulation responses and IL-6 cytokine production, suggesting a modulatory role in Th17 and IL-6 responses implicated in Behçet's disease pathogenesis.

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 prospective study of 568 Chinese non-small-cell lung cancer (NSCLC) patients found that four immune gene polymorphisms were independently associated with survival: IL-5R rs11713419 (5'-UTR, P=0.001), IL23R rs6682925 (5'-FR, P=0.017), TLR1 rs5743551 (5'-FR, P=0.02), and TLR3 rs3775291 (Leu412Phe, P=0.01). Patients carrying 1 unfavorable locus had 124% increased mortality risk (HR=2.24, 95% CI: 1.33-3.75), and those with 2-4 unfavorable loci had 175% increased risk (HR=2.75, 95% CI: 1.67-4.51). Combined SNP and clinical risk score model achieved 5-year AUC of 0.831 versus 0.484 for clinical factors alone.

A case-control study of 1,645 esophageal cancer cases and 1,694 controls in a Chinese population found that IL-23R rs6682925 T>C (adjusted OR=1.23, 95% CI 1.07-1.42) and rs1884444 T>G (adjusted OR=1.16, 95% CI 1.01-1.33) variant genotypes were significantly associated with increased esophageal cancer risk. The associations were independent of smoking and alcohol drinking status.

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).

Meta-analysis of 13 studies (17 comparisons for rs11209026, 12 for rs7530511, 13 for rs2201841) examining IL23R polymorphisms and psoriasis/psoriatic arthritis. rs11209026 (Q381R) A allele showed protective effect for psoriasis (OR 0.616, 95% CI 0.563-0.674) and PsA (OR 0.630, 95% CI 0.524-0.757). rs7530511 (L310P) T allele was protective for psoriasis (OR 0.820, 95% CI 0.764-0.879) and PsA (OR 0.875, 95% CI 0.766-1.000). rs2201841 G allele increased psoriasis risk (OR 1.121, 95% CI 1.031-1.219). No publication bias detected.

This replication study investigated the association of ANTXR2 (rs4333130) and IL-1R2 (rs2310173) polymorphisms with ankylosing spondylitis in a Chinese Han population of 200 cases and 200 controls. Unlike previous findings in Caucasian populations, no significant associations were observed for either variant with AS (rs4333130: p=0.1914, OR=0.713; rs2310173: p=0.0981, OR=0.788), suggesting ethnic genetic heterogeneity in AS susceptibility.

This meta-analysis of 11 studies (13 population samples, 4,668 cases and 5,571 controls) examined IL-23R gene polymorphisms in ankylosing spondylitis susceptibility. The study found rs11209032 (A vs. G: OR=1.173, 95% CI=1.107-1.243, P<0.001) and rs1004819 (OR=1.147, 95% CI=1.022-1.287, P=0.02) as susceptibility alleles, while rs1343151, rs10489629, and rs11209026 were identified as protective variants.

This case-control study in a Chinese Han population evaluated eight IBD susceptibility loci previously identified in European GWAS. The study found that NOD2 P268S contributed to Crohn's disease susceptibility (P=0.025), IL23R rs11805303 conferred protective effect against ulcerative colitis (P=0.010), and PTPN2 rs2542151 was associated with increased UC risk (P=0.001). Phenotype-genotype analysis showed P268S was associated with early-onset disease and ileal involvement in CD patients.

This case-control study in 469 Czech Crohn's disease (CD) patients and 470 controls examined the IBD5 locus, identifying two independent genetic factors: rs6596075 (OR=0.70, protective allele G, p=0.018 in dominant model) and the haplotype tagged by rs2188962 and IGR2063b_1 (OR=1.38 for IGR2063b_1, p=0.00075 in log-additive model). The study demonstrates that these two genetic factors independently contribute to CD susceptibility at the IBD5 locus.

This case-control study examined IL23R gene polymorphisms in 138 Chinese ankylosing spondylitis (AS) patients and 129 controls. Two SNPs showed significant associations: rs6677188 (p<0.001, OR 2.048 for GAC haplotype) and rs11209032 (p<0.001), with the GAC haplotype conferring increased risk. IL23R mRNA expression was significantly elevated in AS patients (0.75±0.25 vs 0.44±0.21, p<0.001), suggesting IL23R involvement in AS susceptibility.

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.

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.

This case-control genetic association study of 206 Thai psoriasis cases and 114 controls validates IL12B and IL23R as psoriasis susceptibility genes in Asian populations. The IL12B SNP rs3212227 showed significant association (OR=1.64, p=0.0058), and haplotype analysis of IL12B SNPs yielded highly significant association (p=0.00081, OR=1.73). IL23R SNP rs7530511 showed marginal significance (p=0.017), while rs11209026 was not polymorphic. The results support the IL23-mediated inflammatory pathway in psoriasis pathogenesis across racial groups despite differences in risk allele frequencies.

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.

This case-control association study examined whether IL-23R gene polymorphisms (rs11209026 p.Arg381Gln, rs41313262 p.Val362Ile, rs11465797 p.Thr175Asn) contribute to susceptibility to acquired aplastic anemia. In 279 AA patients and 184 ethnically matched healthy controls, the three SNP frequencies were similar between groups (rs11209026: 6.1% vs 6.0%, P=0.960; rs41313262: 2.2% vs 1.6%, P=0.958) with no significant difference in serum IL-23 levels, indicating these IL-23R polymorphisms have no apparent impact on aplastic anemia susceptibility.

This case-control study examined polymorphisms in ERAP1 and IL23R genes in a Han Chinese population with ankylosing spondylitis (527 cases, 945 controls). Multiple SNPs in ERAP1 were significantly associated with AS (rs27980 P=0.0048, rs7711564 P=0.0081), confirming the gene's role across different ethnic populations. However, no association was found between IL23R and AS, with the key nonsynonymous SNP rs11209026 not polymorphic in Chinese individuals, suggesting different disease pathogenesis mechanisms between Chinese and Caucasian populations.

This review examines the genetic basis of pediatric inflammatory bowel disease, discussing over 200 identified risk loci from genome-wide association studies and rare monogenic variants affecting susceptibility and progression. The paper highlights major IBD-associated genes including IL23R (rs11209026), NOD2, IL10, and ATG16L1, and proposes that genetic profiling and polygenic risk scores can enable precision medicine approaches for personalized diagnosis and treatment. The paper also discusses how genetic variants in immune, autophagy, and epithelial barrier genes contribute to disease pathogenesis across diverse populations.

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 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 association study tested 5 IL23R SNPs and 12 ATG16L1 SNPs in 380 Korean Crohn's disease patients and 380 controls. Two IL23R variants showed significant associations with CD: rs1004819 (aOR=1.822, P=0.009) and rs1495965 (aOR=1.650, P=0.015), with specificity for stricturing and penetrating disease behavior. None of the 12 ATG16L1 SNPs were significantly associated with CD in this Korean population.

A haplotype association study in 763 Crohn's disease patients and 254 controls showed that IL23R haplotypes account for substantially greater population attributable risk (~10-22%) compared to the single IL23R R381Q variant (~4%). Risk haplotypes in blocks 2 and 3 showed odds ratios of 1.43 and 1.43 respectively, while protective haplotypes showed odds ratios of 0.65 and 0.65, demonstrating IL23R's large contribution to CD susceptibility.

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 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 comprehensive review article traces the evolution of pharmacogenetics from single-gene analysis to whole-genome approaches. It discusses validated pharmacogenetic biomarkers with clinical impact including CYP2D6, CYP2C9, CYP2C19, TPMT, DPD, VKORC1, UGT1A1, and ADRB1/ADRB2, providing examples of how genetic variants affect drug metabolism and response. The paper emphasizes the importance of integrating pharmacogenetic information into clinical practice and drug development.

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 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 of 520 UK patients with psoriatic arthritis (PsA) and 2,260-4,681 controls examined IL23R and IL12B SNPs previously associated with psoriasis. Two IL23R SNPs (rs7530511 and rs11209026) showed borderline association when combined in a haplotype (adjusted p=0.013), while IL12B SNPs (rs3212227 and rs6887695) demonstrated stronger independent associations with PsA susceptibility under a dominant model (OR 1.43 for both). The results suggest these loci are primarily associated with psoriasis rather than PsA-specific arthritis.

This study identified associations between interferon regulatory factor 5 (IRF5) haplotypes and rheumatoid arthritis in a large subgroup of patients, similar to patterns previously found in systemic lupus erythematosus. IRF5 haplotypes represent a significant genetic risk factor for RA susceptibility.

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.

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.

This review summarizes progress in genetics of ankylosing spondylitis (AS), a common complex genetic disease. Key findings include confirmation of IL23R and ERAP1 associations (replicated in multiple populations), characterization of HLA-B27 subtypes with varying disease associations, evidence for non-MHC susceptibility genes, and identification of other MHC class II/III genes and IL-1 complex associations. The study highlights that AS is polygenic with HLA-B27 accounting for only partial genetic risk, and genome-wide association studies are needed to identify additional susceptibility loci.