Kocatepe Tıp Dergisi 3061-9904 Afyonkarahisar Sağlık Bilimleri Üniversitesi 10.18229/kocatepetip.343171 Health Care Administration Sağlık Kurumları Yönetimi ALOPESİ AREATA’DA TNF-α PROMOTÖR POLİMORFİZMİNİN ANALİZİ Ateş Ömer 01 17 2017 18 1 7 12 02 25 2016 04 14 2016 Copyright © 1999, Kocatepe Medical Journal 1999 Kocatepe Medical Journal

AMAÇ: Alopesi Areata patogenezinde, değiş-miş T hücre aracılı bağışıklığın rol aldığını gösterençok sayıda çalışma bulunmaktadır. Sitokinlerinve kemokinlerin Alopesi Areata’nın immunsürecinde önemli rol oynamasından dolayı, AlopesiAreata’ya yatkınlık ile TNF-α-308G/A polimorfizmiarasındaki olası bağlantının Türk populasyonundaaraştırılması amacıyla bu çalışmagerçekleştirildi.GEREÇ VE YÖNTEM: Sunulan vaka kontrol çalışmasına107 Alopesi Areata hastası ve 113sağlıklı kontrol bireyi dahil edildi. TNF-α-308G/Apolimorfizminin genotiplendirmesi PolimerazZincir Reaksiyonu (PZR) ve Restriksiyon EnzimAnalizi (REA) yöntemleri ile gerçekleştirildi.BULGULAR: Hasta ve kontrol gruplarındaTNF-α-308 G/A genotiplerinin ve allel frekanslarınındağılımı arasında anlamlı bir bağlantıbulunamadı (p=0.673 ve p=0.177, sırasıyla).Benzer şekilde, TNF-α-308 G/A polimorfizmi ileAlopesi Areata’nın klinik bulguları arasında farktespit edilemedi.SONUÇ: Bu çalışma, TNF-α-308 G/A polimorfizmininTürk populasyonunda Alopesi Areatagelişiminde önemli bir rol oynamadığını göstermektedir.

 Alopesi Areata Polimorfizm Genetik yatkınlık TNF-α Safavi KH, Muller SA, Suman VJ, Moshell AN, Melton 3rd LJ. Incidence of alopecia areata in Olmsted County, Minnesota,1975 through 1989. Mayo Clin Proc 1995;70:628–33. Madani S, Shapiro J. Alopecia areata update. J Am Acad Dermatol. 2000;42:549–70. De Berker DAR, Messenger AG, Sinclair RD. Disorders of hair. In: Burns T, Breathnach S, Cox N, Griffiths C (Eds). Rook’s Textbook of Dermatology. 7th ed. Oxford: Blackwell Science Ltd; 2004. p.3201–321. de Andrade M, Jackow CM, Dahm N, Hordinsky M, Reveille JD, Duvic M. Alopecia areata in families: association with the HLA locus. J Investig Dermatol Symp Proc 1999;4:220–3. Rodriguez TA, Fernandes KE, Dresser KL, Duvic M; National Alopecia Areata Registry. Concordance rate of alopecia areata in identical twins supports both genetic and environmental factors. J Am Acad Dermatol 2010;62(3):525-7. Todes-Taylor N, Turner R, Wood GS, Stratte PT, Morhenn VB. T cell subpopulations in alopecia areata. J Am Acad Dermatol 1984;11(2 Pt 1):216-23. Whiting DA. Histopathologic features of alopecia areata: a new look. Arch Dermatol 2003;139(12):1555-9. Ito T, Tokura Y. The role of cytokines and chemokines in the T-cell mediated autoimmune process in alopecia areata. Exp Dermatol. 2014;23:787–91. Islam N, Leung PS, Huntley AC, Gershwin ME. The autoimmune basis of alopecia areata: a comprehensive review. Autoimmun Rev. 2015;14(2):81-9. Tembhre MK, Sharma VK. T-helper and regulatory T-cell cytokinesin the peripheral blood of patients with active alopecia areata. Br J Dermatol. 2013;169:543–8. Beutler B, Cerami A. The biology of cachectin/TNF-A primary mediator of the host response. Annu Rev Immunol 1989;7:625 Kroeger KM, Steer JH, Joyce DA, Abraham LJ. Effects of stimulus and cell type on the expression of the -308 tumour necrosis factor promoter polymorphism. Cytokine. 2000;12(2):110-9. Bouma G, Crusius JB, Oudkerk Pool M, et al. Secretion of tumour necrosis factor alpha and lymphotoxin alpha in relation to polymorphisms in the TNF genes and HLA-DR alleles: relevance for inflammatory bowel disease. Scand J Immunol 1996;43:456–463 Kroeger KM, Carville KS, Abraham LJ. The -308 tumour necrosis factor-alpha promoter polymorphism effects transcription. Mol Immunol 1997;34:391–9. Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW. Effects of a polymorphism in the human tumor necrosis factor a promoter on transcriptional activation. Proc Natl Acad Sci U S A 1997;94:3195–9. Rossi A, Cantisani C, Carlesimo M, et al. Serum concentrations of IL-2, IL-6, IL-12 and TNF-α in patients with alopecia areata. Int J Immunopathol Pharmacol. 2012;25(3):781-8. Atwa MA, Youssef N, Bayoumy NM. T-helper 17 cytokines (interleukins 17, 21, 22, and 6, and tumor necrosis factor-α) in patients with alopecia areata: association with clinical type and severity. Int J Dermatol. 2015 Jul 31. doi: 10.1111/ijd.12808. [Epub ahead of print] Bilgic O, Sivrikaya A, Unlu A, Altinyazar HC. Serum cytokine and chemokine profiles in patients with alopecia areata. J Dermatolog Treat. 2016;27(3):260-3. Kasumagic-Halilovic E, Prohic A, Cavaljuga S. Tumor necrosis factor-alpha in patients with alopecia areata. Indian J Dermatol. 2011;56(5):494-6. Galbraith GM, Pandey JP. Tumor necrosis factor alpha (TNFalpha) gene polymorphism in alopecia areata. Hum Genet. 1995;96(4):433-6. Redler S, Albert F, Brockschmidt FF,et al. Investigation of selected cytokine genes suggests that IL2RA and the TNF/LTA locus are risk factors for severe alopecia areata. Br J Dermatol. 2012;167(6):1360-5. Tauber M, Buche S, Reygagne P et al. Groupe de Recherche sur Psoriasis de Société Française de, Dermatologie; Club Rhumatismes et Inflammation (CRI); Groupe d’études thérapeutiques des affections inflammatoires du tube digestif (GETAID). Alopecia areata occurring during anti-TNF therapy: a national multicenter prospective study. J Am Acad Dermatol. 2014;70(6):1146-9. Nie G, Qi JH, Huang CW, Yang T, Shi N, Chen YJ. Meta-analysis of the TNF-α-308G/A polymorphism and vitiligo risk. Genet Mol Res. 2015;14(4):17296-304. Kalkan G, Ateş O, Karakuş N, Sezer S. Functional polymorphisms in cell death pathway genes FAS and FAS ligand and risk of alopecia areata. Arch Dermatol Res. 2013;305(10):909- 15. Olsen EA, Hordinsky MK, Price VH et al. Alopecia areata investigational assessment guidelines-part II. National alopecia areata foundation. J Am Acad Dermatol 2004;51:440–447 Nicholson LB, Kuchroo VK. Manipulation of the Th1/ Th2 balance in autoimmune disease. Curr Opin Immunol 1996;8:837–842 Barahmani N, Lopez A, Babu D, et al. Serum T helper 1 cytokine levels are greater in patients with alopecia areata regardless of severity or atopy. Clin Exp Dermatol. 2010;35:409– 16. Teraki Y, Imanishi K, Shiohara T. Cytokines in alopecia areata: contrasting cytokine profiles in localized form and extensive form (alopecia universalis). Acta Derm Venereol. 1996;76:421–3. Ates O, Musellim B, Ongen G, Topal-Sarıkaya A. Interleukin-10 and Tumor Necrosis Factor-α Gene Polymorphisms in Tuberculosis. Journal of Clinical Immunology 2008;28:232-236. Ates O, Gulen H, Hamuryudan V, Topal-Sarıkaya A. Tumor Necrosis Factor-Alpha and Interleukin 10 Gene Promoter Polymorphismsm in Turkish Rheumatoid Arthritis Patients. Clinical Rheumatology 2008;27:1243-1248 Ates O, Musellim B, Ongen G, Topal-Sarıkaya A. Analyses of TNF polymorphisms in Turkish systemic sclerosis patients with interstitial lung involvement. Biochemical Genetics 2008;46:696-701 Ates O, Dalyan L, Hatemi G, Hamuryudan V, Topal-Sarıkaya A. Analyses of functional IL10 and TNF- α genotypes in Behçet’s Syndrome. Molecular Biology Reports 2010;37:3637-3641 Ates O, Kurt S, Altinisik J, Bozkurt N, Karaer H. Genetic variations in Tumor Necrosis Factor alpha, Interleukin 10 genes and migraine susceptibility. Pain Medicine 2011:12:1464-1469 Akman A, Sallakcı N, Coskun M, et al. TNF- TNF-a gene 1031 T/C polymorphism in Turkish patients with Behçet’s disease. Br J Dermatol 2006;155:350–6.