Alopesi Areata’da IL–17 Promotör Polimorfizminin (-152 G/A) Araştırılması

Amaç: T- hücre aracılı otoimmün bir hastalık olan Alopesi areata (AA)’nın patogenezinde T helper 17 hücreleri (Th17) önemli bir rol oynamaktadır. Önceki çalışmalar AA’lı hastalarda, Th17 hücreleri tarafından üretilen interlökin (IL)–17’nin ekspresyonunun kontrol grubuna göre anlamlı düzeyde yüksek olduğunu göstermiştir. Bu çalışmanın amacı IL–17 -152 G/A promotör polimorfizmi ile AA’nın ilişkisinin olup olmadığını değerlendirmekti. Gereç ve Yöntem: Sunulan bu çalışmada, Polimeraz Zincir Reaksiyonu (PZR) ve Restriksiyon Enzim Analizi (REA) yöntemleri kullanılarak 188 AA hastasında ve 168 sağlıklı bireyde IL–17 geni -152 G/A polimorfizminin genotip ve allel dağılımı analiz edildi. Bulgular: Hasta ve kontrol grupları arasında IL–17 geni -152 G/A promotör polimorfizminin genotip dağılımı istatistiksel olarak anlamlı derecede farklı bulundu (p=0.0300). Ancak IL–17 -152 G/A polimorfizminin allel frekanslarının dağılımı istatistiksel olarak anlamlı bulunmadı (p=0.160). Sonuç: Bizim sonuçlarımız, IL–17 -152G/A promotör polimorfizminin AA ile ilişkili olabileceğini göstermektedir.

Investigation of IL–17 promoter polymorphism (-152 G/A) in alopecia areata

Objectives: T helper 17 cells (Th17) play an important role in the pathogenesis of Alopecia areata (AA), which is a T-cell mediated autoimmune disease. Previous studies showed significantly increased expression of interleukin (IL)–17, which product from Th17 cells, levels in AA patients compared to healthy controls. The aim of present study was to assess whether IL–17 -152 G/A promoter polymorphism is associated with AA. Material and Methods: The present study analyzed the genotype distribution and allele frequency for the IL–17 -152 G/A promoter polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique in 188 AA patients and 168 healthy individuals. Results: Genotype distribution of the IL–17 -152 G/A polymorphism was found to be significantly different between patients and controls (p=0.0300). However allele frequencies of the IL–17 -152 G/A polymorphism were not found to be significantly different between patients and controls (p=0.160). Conclusion: Our results suggested that promoter region polymorphism -152G/A of IL–17 gene was associated with AA.

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  • 1. Xing L, Dai Z, Jabbari A, Cerise JE, Higgins CA, Gong W, et al. Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med. 2014; 20(9):1043–1049.
  • 2. Dai Z, Xing L, Cerise J, Wang EH, Jabbari A, de Jong A, et al.CXCR3 Blockade Inhibits T Cell Migration into the Skin and Prevents Development of Alopecia Areata. J Immunol 2016; 197(4):1089-99.
  • 3. Kim SK, Park HJ, Chung JH, Kim JW, Seok H, Lew BL, et al. Association Between Interleukin 18 Polymorphisms and Alopecia Areata in Koreans. Journal Of Interferon & Cytokıne Research 2014;34( 5).
  • 4. Han YM, Sheng YY, Xu F, Qi SS, Liu XJ, Hu RM, et al. Imbalance of T-helper 17 and regulatory T cells in patients with alopecia areata. Journal of Dermatology 2015; 42: 981–988.
  • 5. Zhang X, Zhao Y, Ye Y, Li S, Qi S, Yang Y, et al. Lesional infiltration of mast cells, Langerhans cells, T cells and local cytokine profiles in alopecia areata. Arch Dermatol Res 2015; 307:319–331.
  • 6. Bodemer C, Peuchmaur M, Fraitaig S, Chatenoud L, Brousse N, Prost Y. Role of Cytotoxic T Cells in Chronic Alopecia Areata. J Invest Dermatol 2000; 114: 112–116.
  • 7. Chen J, Deng Y, Zhao J, Luo Z, Peng W, Yang J, et al. The Polymorphism of IL-17 G-152A was Associated with Childhood Asthma and Bacterial Colonization of the hypopharynx in bronchiolitis. J Clin Immunol 2010; 30:539–545.
  • 8. Kim BS, Park YJ, Chung Y. Targeting IL-17 in autoimmunity and inflammation. Arch. Pharm. Res. DOI 10.1007/s12272-016-0823-8.
  • 9. Aytekin N, Akcali C, Pehlivan S, Kirtak N, Inaloz S. Investigation of interleukin-12, interleukin-17 and interleukin-23 receptor gene polymorphisms in alopecia areata. Journal of International Medical Research 2015; 43(4): 526–534.
  • 10. Elela MA, Gawdat HI, Hegazy RA, Fawzy MM, Abdel Hay RM, Saadi D, et al. B cell activating factor and T-helper 17 cells: possible synergistic culprits in the pathogenesis of Alopecia Areata. Arch Dermatol Res. 2016; 308:115–121.
  • 11. Tojo G, Fujimura T, Kawano M, Ogasawara K, Kambayashi Y, Furudate S, et al. Comparison of Interleukin-17- Producing Cells in Different Clinical Types of Alopecia Areata. Dermatology 2013;227:78–82.
  • 12. Atwa MA, Youssef N, Bayoumy NM. T-helper 17 cytokines (interleukins 17, 21, 22, and 6, and tumor necrosis factor-a) in patients with alopecia areata: association with clinical type and severity. International Journal of Dermatology 2016; 55: 666–672.
  • 13. Lew BL, Cho HR, Haw S, Kim HJ, Chung JH, Sim WY. Association between IL17A/IL17RA Gene Polymorphisms and Susceptibility to Alopecia Areata in the Korean Population. Ann Dermatol. 2012;24(1):61-5.
  • 14. Alli R, Nguyen P, Boyd K, Sundberg JP, Geiger TL. A mouse model of clonal CD8(+) T lymphocyte-mediated alopecia areata progressing to alopecia universalis. J Immunol 2012; 188: 477–486.
  • 15. Ito T, Tokura Y. The role of cytokines and chemokines in the T-cell-mediated autoimmune process in alopecia areata. Experimental Dermatology, 2014; 23: 787–791.