Investigating the Role of IL-17A gene rs2275913 Variant in Rosacea: In Silico Analysis Suggests Further Studies

Yıl 2024, Cilt: 11 Sayı: 3, 139 - 144, 18.12.2024

Ali Çağatay Can Coşkun , Suzan Demir Pektaş , Çilem Özdemir , Ayşegül Demirtaş Bilgiç , Murat Cenik , Tuba Edgünlü

https://doi.org/10.47572/muskutd.1469931

Öz

Interleukine-17 (IL-17), a crucial component of the body's immune response against pathogens, is also implicated in various inflammatory processes. Notably, the skin of rosacea patients exhibits chronic inflammation, and IL-17 is known to induce the production of additional pro-inflammatory chemokines and cytokines. This inflammatory cascade can contribute to the hallmark features of rosacea, including dilated blood vessels, immune cell infiltration, and the development of papules and pustules. The study aimed to examine whether a specific genetic variation in the IL-17A gene (-197 G>A; rs2275913) is associated with rosacea susceptibility. We compared the IL-17A variant and rosacea risk in 31 healthy individuals and 25 with rosacea. Genotyping of the IL-17A variant was performed using the PCR-RFLP method. Genotype and allele frequency distributions were compared across groups using the chi-square test (χ2). Additionally, gene ontology (GO) analysis of the IL-17A gene using web-based tools is also demonstrated. No significant association between the rs2275913 polymorphism and rosacea susceptibility was observed in this study (p=0.124) but in silico analysis suggested that the IL-17A gene interaction network might play a role in the disease. Given its critical function in regulating IL-17A and related genes, particularly in immune defense and inflammatory processes, further investigation into its potential influence on rosacea development is required.

Anahtar Kelimeler

IL-17A, Inflammatory Cytokines, Gene Polymorphism, Rosacea

Proje Numarası

1919B012101920

Rosacea'da IL-17A geni rs2275913 Varyantının Rolünün Araştırılması: In Silico Analiz Önerileri

Öz

Vücudun patojenlere karşı bağışıklık tepkisinin önemli bir bileşeni olan İnterlökin-17 (IL-17), çeşitli inflamatuar süreçlerde rol oynar. Özellikle rosacea hastalarının derisi kronik inflamasyon sergiler ve IL-17'nin ek proinflamatuar kemokinler ve sitokinlerin üretimini indüklediği bilinmektedir. Bu inflamatuar kaskad, genişlemiş kan damarları, bağışıklık hücresi infiltrasyonu ve papül ve püstüllerin gelişimi dahil olmak üzere rosacea'nın ayırt edici özelliklerine katkıda bulunabilir. Çalışmada IL-17A genindeki spesifik bir genetik varyasyonun (-197 G>A; rs2275913) rosacea duyarlılığı ile ilişkili olup olmadığının incelenmesi amaçlandı. IL-17A varyantını ve rosacea riskini 31 sağlıklı bireyde ve rosacealı 25 bireyde karşılaştırdık. IL-17A varyantının genotiplemesi PCR-RFLP yöntemi kullanılarak yapıldı. Genotip ve alel frekans dağılımları gruplar arasında ki-kare testi (χ2) kullanılarak karşılaştırıldı. Ek olarak, web tabanlı araçlar kullanılarak IL-17A geninin gen ontolojisi (GO) analizi de gösterilmektedir. Bu çalışmada rs2275913 polimorfizmi ile rosacea duyarlılığı arasında anlamlı bir ilişki gözlenmedi (p=0.124), ancak in silico analizi IL-17A gen etkileşim ağının hastalıkta rol oynayabileceğini düşündürdü. IL-17A'nın ve ilgili genlerin, özellikle de bağışıklık savunması ve inflamatuar süreçlerdeki düzenlenmesindeki kritik işlevi göz önüne alındığında, rosacea gelişimi üzerindeki potansiyel etkisinin daha fazla araştırılması gerekmektedir.

Anahtar Kelimeler

IL-17A, İnflamatuar Sitokinler, Gen Polimorfizmi, Rosacea

Destekleyen Kurum

Scientific and Technological Research Council of Turkey (TUBITAK)

Proje Numarası

1919B012101920

Kaynakça

• Buddenkotte J, Steinhoff M. Recent advances in understanding and managing rosacea. F1000Research. 2018;7.
• Neogi T. Clinical Practice: Gout. N Engl J M. 2011;364(5):443–52.
• Ahn CS, Huang WW. Rosacea Pathogenesis. Dermatologic Clinics. 2018;36(2):81–6.
• Kellen R, Silverberg NB. Pediatric rosacea. Cutis. 2016;98(1):49–53.
• Yang J, Sundrud MS, Skepner J, et al. Targeting Th17 cells in autoimmune diseases. Trends Pharmacol Sci. 2014;35(10):493–500.
• Miossec P, Kolls JK. Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov. 2012;11(10):763–76.
• Yasuda K, Takeuchi Y, Hirota K. The pathogenicity of Th17 cells in autoimmune diseases. Semin Immunopathol. 2019;41(3):283–97.
• Buhl T, Sulk M, Nowak P, et al. Molecular and morphological characterization of inflammatory infiltrate in rosacea reveals activation of Th1/Th17 pathways. J Invest Dermatol. 2015;135(9):2198–208.
• Gallo RL, Granstein RD, Kang S, et al. Standard classification and pathophysiology of rosacea: The 2017 update by the National Rosacea Society Expert Committee. J Am Acad Dermatol. 2018;78(1):148–55.
• Steinhoff M, Schauber J, Leyden JJ. New insights into rosacea pathophysiology: A review of recent findings. J Am Acad Dermatol. 2013;69(6):S15–26.
• Rainer BM, Kang S, Chien AL, et al. Rosacea: Epidemiology, pathogenesis, and treatment. Dermatoendocrinol. 2017;9(1):e1361574.
• Xu M, Lu H, Lee YH, et al. An Interleukin-25-mediated autoregulatory circuit in keratinocytes plays a pivotal role in psoriatic skin inflammation. Immunity. 2018;48(4):787-98.e4.
• Johansen C, Usher PA, Kjellerup RB, et al. Characterization of the interleukin‐17 isoforms and receptors in lesional psoriatic skin. Br J Dermatol. 2009;160(2):319–24.
• Reich K, Sullivan J, Arenberger P, et al. Secukinumab shows high and sustained efficacy in nail psoriasis: 2.5‐year results from the randomized placebo‐controlled TRANSFIGURE study. Br J Dermatol. 2021;184(3):425–36.
• Feldmeyer L, Mylonas A, Demaria O, et al. Interleukin 23–Helper T Cell 17 axis as a treatment target for pityriasis rubra pilaris. JAMA Dermatol. 2017;153(4):304–8.
• Zhou Y, Hou W, Xu K, et al. The elevated expression of Th17-related cytokines and receptors is associated with skin lesion severity in early systemic sclerosis. Hum Immunol. 2015;76(1):22–9.
• Klonowska J, Gleń J, Nowicki RJ, et al Combination of FLG mutations and SNPs of IL-17A and IL-19 influence on atopic dermatitis occurrence. Postepy Dermatol Alergol. 2022;39(1):200-8.
• Narbutt J, Wojtczak M, Zalińska A, et al. The A/A genotype of an interleukin‐17A polymorphism predisposes to increased severity of atopic dermatitis and coexistence with asthma. Clin Exp Dermatol. 2015;40(1):11–6.
• Sanad EMK, Nazmy NN, Abd-El Hamid El Sayed R, et al. Interleukin-17A gene single nucleotide polymorphism and its relation to fungal growth in psoriatic patients: A preliminary study. J Cosmet Dermatol. 2022;21(7):3059–67.
• Kaur R, Rawat AK, Kumar S, et al. Association of genetic polymorphism of interleukin-17A & interleukin-17F with susceptibility of psoriasis. Indian J Med Res. 2018;148(4):422-6.
• Zapata-Salazar NA, Kubelis-Lopez DE, Salinas-Santander MA, et al. Association of rs4711998 of IL-17A, rs2275913 of IL-17A and rs763780 IL-17F gene polymorphisms with non-segmental vitiligo in a Mexican population. Arch Dermatol Res. 2023;315(3):447–54.