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<p>Ankylosing spondylitis (AS) is linked to HLA-B27. But non-HLA genes like ERAP1(Endoplasmic Reticulum Aminopeptidase 1) and pro-inflammatory cytokines IL-23/IL-17 also contributes significantly to disease susceptibility and activity. We evaluated the ERAP1 rs27038 polymorphism and serum IL-17A in Indian AS patients. In this case–control study, 75 radiographic AS patients and 72 matched healthy controls were recruited. Serum IL-17A was measured by ELISA, and ERAP1 rs27038 was genotyped by Sanger sequencing. Disease activity (BASDAI, ASDAS-CRP) and standard labs (ESR, CRP) were recorded. Statistical analyses compared groups, assessed allele frequencies (OR), and ROC AUC for IL-17&#xa0;A. AS patients had significantly higher IL-17A (median 48.4 pg/mL, IQR 9.8–191.4) than controls (8.84 pg/ml, IQR: 7.64–24.77, <i>p</i> = 0.0002). HLA-B27 was positive in 77% of AS patients. ERAP1 rs27038 GA genotype frequency was elevated in AS cases (33.8%) versus controls (19.4%), yielding OR: 2.18 (95%CI: 1.01–4.68, <i>p</i> = 0.04) and also in dominant model (GG vs. GA+AA) OR: 2.08 (95%CI: 1.02–4.27, <i>p</i> = 0.042). Although not statistically significant, the frequency of “A” allele was higher in AS patients (22%) as compared to control (14%). AS patients with homozygous for the “A” allele had higher IL-17A than G-allele carriers (<i>p</i> = 0.017). IL-17A correlated modestly with hsCRP (ρ = 0.35, <i>p</i> &lt; 0.001), but not with BASDAI or ASDAS. The IL-17A ROC AUC for distinguishing AS was 0.848 (95% CI 0.755–0.917). In multivariate analysis, HLA-B27 positivity and ESR (but not IL-17&#xa0;A) remained independent predictors of AS. These findings support an association between ERAP1 variation, HLA-B27, and IL-17-mediated inflammation in AS, although causal relationships require further investigation.</p>

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ERAP1 rs27038 Polymorphism and IL-17A in Radiographic Axial Spondyloarthritis: A South Indian Case–Control Study

  • 期刊论文

  • 发表日期：

    2026年7月29日

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  • Husna Fatima,
  • Meghna Gavali,
  • Bhavya Sirivelu,
  • Noorjahan Mohammad,
  • Iyyapy Krishna Mohan,
  • Vijay Kumar Kutala

摘要

Ankylosing spondylitis (AS) is linked to HLA-B27. But non-HLA genes like ERAP1(Endoplasmic Reticulum Aminopeptidase 1) and pro-inflammatory cytokines IL-23/IL-17 also contributes significantly to disease susceptibility and activity. We evaluated the ERAP1 rs27038 polymorphism and serum IL-17A in Indian AS patients. In this case–control study, 75 radiographic AS patients and 72 matched healthy controls were recruited. Serum IL-17A was measured by ELISA, and ERAP1 rs27038 was genotyped by Sanger sequencing. Disease activity (BASDAI, ASDAS-CRP) and standard labs (ESR, CRP) were recorded. Statistical analyses compared groups, assessed allele frequencies (OR), and ROC AUC for IL-17 A. AS patients had significantly higher IL-17A (median 48.4 pg/mL, IQR 9.8–191.4) than controls (8.84 pg/ml, IQR: 7.64–24.77, p = 0.0002). HLA-B27 was positive in 77% of AS patients. ERAP1 rs27038 GA genotype frequency was elevated in AS cases (33.8%) versus controls (19.4%), yielding OR: 2.18 (95%CI: 1.01–4.68, p = 0.04) and also in dominant model (GG vs. GA+AA) OR: 2.08 (95%CI: 1.02–4.27, p = 0.042). Although not statistically significant, the frequency of “A” allele was higher in AS patients (22%) as compared to control (14%). AS patients with homozygous for the “A” allele had higher IL-17A than G-allele carriers (p = 0.017). IL-17A correlated modestly with hsCRP (ρ = 0.35, p < 0.001), but not with BASDAI or ASDAS. The IL-17A ROC AUC for distinguishing AS was 0.848 (95% CI 0.755–0.917). In multivariate analysis, HLA-B27 positivity and ESR (but not IL-17 A) remained independent predictors of AS. These findings support an association between ERAP1 variation, HLA-B27, and IL-17-mediated inflammation in AS, although causal relationships require further investigation.