ALOPESİ AREATA’DA TNF-α PROMOTÖR POLİMORFİZMİNİN ANALİZİ
AMAÇ: Alopesi Areata patogenezinde, değiş- miş T hücre aracılı bağışıklığın rol aldığını gösteren çok sayıda çalışma bulunmaktadır. Sitokinlerin ve kemokinlerin Alopesi Areata’nın immun sürecinde önemli rol oynamasından dolayı, Alopesi Areata’ya yatkınlık ile TNF-α-308G/A polimorfizmi arasındaki olası bağlantının Türk populasyonunda araştırılması amacıyla bu çalışma gerçekleştirildi. GEREÇ VE YÖNTEM: Sunulan vaka kontrol çalışmasına 107 Alopesi Areata hastası ve 113 sağlıklı kontrol bireyi dahil edildi. TNF-α-308G/A polimorfizminin genotiplendirmesi Polimeraz Zincir Reaksiyonu (PZR) ve Restriksiyon Enzim Analizi (REA) yöntemleri ile gerçekleştirildi. BULGULAR: Hasta ve kontrol gruplarında TNF-α-308 G/A genotiplerinin ve allel frekanslarının dağılımı arasında anlamlı bir bağlantı bulunamadı (p=0.673 ve p=0.177, sırasıyla). Benzer şekilde, TNF-α-308 G/A polimorfizmi ile Alopesi Areata’nın klinik bulguları arasında fark tespit edilemedi. SONUÇ: Bu çalışma, TNF-α-308 G/A polimorfizminin Türk populasyonunda Alopesi Areata gelişiminde önemli bir rol oynamadığını göstermektedir.
___
- 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.