Association of IL-23/IL-17 Pathway-Related Gene Polymorphisms with Idiopathic Scleritis in Chinese Han Population

To examine the relationship between IL-23/IL-17 pathway gene polymorphisms and scleritis susceptibility in the Chinese Han population. We assessed IL-23/IL-17 pathway-related SNPs in 898 scleritis cases and 1,573 controls, employing stratified analysis to evaluate subtype-specific impacts and a discovery-validation cohort strategy to ensure genetic association reliability. IL-23 R/rs10789229 TC genotype and C allele, and the IL-21/rs2221903 TT genotype and T allele were more frequent in scleritis patients (Pc = 2.07 × 10⁻³-2.77 × 10⁻⁶, OR = 1.497–2.327, 95% CI = 1.216–3.219), particularly anterior scleritis (Pc = 3.88 × 10⁻³-2.95 × 10⁻⁶, OR = 1.507–2.378, 95% CI = 1.209–3.321). The IL-23 R/rs10789229 TT genotype and T allele, and the IL-21/rs2221903 TC genotype and C allele were found less common among scleritis patients overall (Pc = 2.07 × 10⁻³-4.18 × 10⁻⁶, OR = 0.436–0.668, 95% CI = 0.316–0.822) and in the anterior scleritis subgroups (Pc = 3.88 × 10⁻³-4.43 × 10⁻⁶, OR = 0.427–0.664, 95% CI = 0.306–0.827). The analysis of haplotypes showed a noteworthy surge of IL-23 R CCCG haplotype in both scleritis patients in general (Pc = 1.91 × 10⁻⁴) and those with anterior scleritis (Pc = 1.15 × 10⁻⁴). Conversely, the frequency of the IL-17A GAA haplotype was significantly lower among scleritis patients overall (Pc = 4.17 × 10⁻¹²) and in the anterior or posterior scleritis subgroups (Pc = 7.41 × 10⁻¹¹; Pc = 0.021). Only the IL-23 R/rs10789229 variant demonstrated consistent replication in the validation cohort. The findings suggest that specific polymorphisms of IL-23/IL-17 pathway-related genes could confer risk to the development of scleritis in the Chinese Han population. Patients with varying subtypes of scleritis exhibit somewhat similar genetic profiles.