rs1495965

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.

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.

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.

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 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 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 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 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.

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 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.

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 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.