rs1004819

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 PhD thesis encompasses multiple studies on pediatric inflammatory bowel disease (IBD): epidemiological analysis shows rising incidence in Scotland (4.45 to 7.82 per 100,000 per year); transmission disequilibrium testing identified rs8126734-A as overtransmitted in IBD and CD (OR 1.48, p=0.047; OR 1.85 for CD, p=0.008); genome-wide association meta-analysis confirmed strong signals in ICOSLG 3'UTR for CD susceptibility; CRP gene variants (rs1417938, rs1130864) showed significant overtransmission (p=0.006, p=0.015); and faecal calprotectin demonstrated superior diagnostic accuracy for PIBD detection (sensitivity 0.93, specificity 0.74).

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).

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 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 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 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 of 763 Crohn's disease cases and 254 healthy controls investigated 10 genes in the IL23/IL17 pathway, identifying novel haplotype associations in IL17A (p=0.02), IL17RA (p=0.001), IL17RD (p=0.001), IL12RB1 (p=0.003), and IL12RB2 (p=0.001). Combined risk haplotypes from multiple pathway genes showed cumulative effect with OR=4.3 for 5 risk haplotypes (p=1.7×10⁻⁷), and significant epistatic interactions were observed between IL17A and IL23R variants (p=0.047) and between IL17RA and IL23R variants (p=0.036).

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 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.

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.

A case-control study of 217 Crohn's disease, 252 ulcerative colitis, and 290 control patients in Hungary examining associations with IBD5 locus variants. The IGR2096a_1 T allele (rs12521868) and IGR2198a_1 C allele (rs11739135) showed significantly increased frequencies in Crohn's disease (47.2% and 45.9% vs 38.2% and 37.7% in controls, p<0.05) and were independent risk factors (OR=1.748, 95% CI 1.186-2.574 for T allele; OR=1.646, 95% CI 1.119-2.423 for C allele), while SLC22A4 C1672T and SLC22A5 G-207C variants showed no association.

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.

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.

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.