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Background <p>Vitiligo is an autoimmune disorder primarily categorized into non-segmental (NSV) and segmental (SV) subtypes. Interleukin-21 (IL-21) is a pleiotropic cytokine implicated in immune dysregulation.</p> Objective <p>To investigate the association of serum IL-21 levels and two genetic variants (rs2055979 and rs4833837) with susceptibility to NSV and SV in an Iranian cohort.</p> Methods <p>The study included 264 vitiligo patients (225 NSV, 39 SV) and up to 390 healthy controls. Serum IL-21 was measured by ELISA. Genotyping for rs2055979 was performed by RFLP-PCR, and for rs4833837 by ASO-PCR.</p> Results <p>Serum IL-21 levels were significantly elevated in both NSV (median 71.50 pg/mL) and SV (median 65.35 pg/mL) patients compared to controls (median 18.70 pg/mL; <i>p</i> &lt; 0.0001). For rs2055979, the GT genotype was associated with increased risk of NSV (unadjusted OR = 2.99, 95% CI = 1.86–4.80, <i>p</i> &lt; 0.0001; age- and sex-adjusted OR = 1.809, 95% CI = 1.061–3.085, <i>p</i> = 0.029) and SV (unadjusted OR = 4.29, 95% CI = 1.45–12.7, <i>p</i> = 0.005; adjusted OR = 3.486, 95% CI = 1.006–12.077, <i>p</i> = 0.049). The unadjusted G allele was a risk factor for NSV (OR = 1.52, 95% CI = 1.19–1.94, <i>p</i> = 0.0009) but not for SV (<i>p</i> = 0.09). The GG genotype also conferred elevated unadjusted risk for NSV (OR = 2.51, 95% CI = 1.44–4.37, <i>p</i> = 0.0009). In contrast, rs4833837 showed no significant association with either vitiligo subtype.</p> Conclusion <p>The IL-21 rs2055979 polymorphism is associated with vitiligo susceptibility, with the GT genotype representing a risk factor for both NSV and SV after adjustment for age and sex. The marked elevation of serum IL-21 in both NSV and SV further supports a pathogenic role for IL-21, suggesting the IL-21/IL-21R axis as a potential therapeutic target.</p>

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IL-21 rs2055979 and serum IL-21 levels are associated with both non-segmental and segmental vitiligo in an Iranian cohort

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月18日

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  • Nasser Gholijani,
  • Zeinab Dehghan,
  • Samira Sadat Abolmaali,
  • Atefe Ghamar Talepoor,
  • Mohammadreza Yazdani,
  • Gholamreza Daryabor

摘要

Background

Vitiligo is an autoimmune disorder primarily categorized into non-segmental (NSV) and segmental (SV) subtypes. Interleukin-21 (IL-21) is a pleiotropic cytokine implicated in immune dysregulation.

Objective

To investigate the association of serum IL-21 levels and two genetic variants (rs2055979 and rs4833837) with susceptibility to NSV and SV in an Iranian cohort.

Methods

The study included 264 vitiligo patients (225 NSV, 39 SV) and up to 390 healthy controls. Serum IL-21 was measured by ELISA. Genotyping for rs2055979 was performed by RFLP-PCR, and for rs4833837 by ASO-PCR.

Results

Serum IL-21 levels were significantly elevated in both NSV (median 71.50 pg/mL) and SV (median 65.35 pg/mL) patients compared to controls (median 18.70 pg/mL; p < 0.0001). For rs2055979, the GT genotype was associated with increased risk of NSV (unadjusted OR = 2.99, 95% CI = 1.86–4.80, p < 0.0001; age- and sex-adjusted OR = 1.809, 95% CI = 1.061–3.085, p = 0.029) and SV (unadjusted OR = 4.29, 95% CI = 1.45–12.7, p = 0.005; adjusted OR = 3.486, 95% CI = 1.006–12.077, p = 0.049). The unadjusted G allele was a risk factor for NSV (OR = 1.52, 95% CI = 1.19–1.94, p = 0.0009) but not for SV (p = 0.09). The GG genotype also conferred elevated unadjusted risk for NSV (OR = 2.51, 95% CI = 1.44–4.37, p = 0.0009). In contrast, rs4833837 showed no significant association with either vitiligo subtype.

Conclusion

The IL-21 rs2055979 polymorphism is associated with vitiligo susceptibility, with the GT genotype representing a risk factor for both NSV and SV after adjustment for age and sex. The marked elevation of serum IL-21 in both NSV and SV further supports a pathogenic role for IL-21, suggesting the IL-21/IL-21R axis as a potential therapeutic target.