HACI ÖMER ATEŞ

Alopesi areata'da IL-6 Promotör Polimorfizmi

Amaç: Alopesi areata (AA), T- hücre aracılı otoimmün bir hastalıktır ve sitokinler bu hastalığın gelişiminde önemli rol oynamaktadırlar. Önceki çalışmalar AA'lı hastaların serumlarında proinflamatuar bir sitokin olan IL-6'nın serum seviyesinin kontrol grubuna göre anlamlı düzeyde yüksek olduğunu göstermiştir. IL-6 geninin promotör bölgesinde bulunan -174 G/C polimorfizmi IL-6'nın serum seviyesini etkilemektedir. Sunulan bu çalışmanın amacı IL-6 -174 G/C promotör polimorfizmi ile AA'nın ilişkisinin olup olmadığını değerlendirmekti. Yöntemler: Bu çalışmaya 146 AA'lı hasta ve 133 sağlıklı birey dahil edildi. IL-6 geni -174 G/C polimorfizminin genotiplendirmesi Polimeraz Zincir Reaksiyonu (PZR) ve Restriksiyon Enzim Analizi (REA) yöntemleri ile gerçekleştirildi. Bulgular: Hasta ve kontrol grupları arasında IL-6 geni -174 G/C promotör polimorfizminin genotip ve allel frekanslarının dağılımı istatistiksel olarak anlamlı bulunmadı (sırasıyla, p=0.749 ve p=0.228). Sonuç: Bu çalışma, IL-6 -174G/C polimorfizminin AA için bir yatkınlık faktörü olmadığını göstermektedir.

IL-6 Promoter Polymorphism in Alopecia Areata

Objectives: Alopecia areata (AA) is a T-cell mediated autoimmune disease and cytokines play important roles development of this disease. Previous studies showed significantly increased serum IL-6, as a pro-inflammatory cytokine, levels in AA patients compared to healthy controls. The -174G/C polymorphism in the promoter of the IL-6 gene that affects IL-6 serum levels. The aim of present study was to assess whether IL-6 -174G/C promoter polymorphism is associated with AA. Methods: The study included 146 unrelated patients with AA and 133 unrelated healthy controls. The genotyping of IL-6 gene 174 G/C polymorphism was performed by polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP) analysis. Results: Genotype and allele distribution of IL-6 gene -174 G/C polymorphism was not found to be significantly different between patients and controls (p=0.749 and p=0.228, respectively). Conclusion: This study shows that IL-6 gene -174 G/C polymorphism is not a predisposing factor for AA.

PDF

___

1. Seok H, Suh DW, Jo B, Lee HB, Jang HM, Park HK. Association between TLR1 polymorphisms and alopecia areata. Autoimmunity 2014;1-6.
2. Kim SK, Park HJ, Chung JH, et al. Association Between Interleukin 18 Polymorphisms and Alopecia Areata in Koreans. Journal Of Interferon & Cytokıne Research 2014;34.
3. Jabbari A, Petukhova L, Cabral RM, et al. Genetic basis of alopecia areata: A roadmap for translational research. Dermatol Clin. 2013;31:109-17.
4. Cork MJ, Crane AM, Duff GW. Genetic control of cytokines. Cytokine gene polymorphisms in alopecia areata. Dermatol Clin. 1996;14:671-8.
5. de Andrade M, Jackow CM, Dahm N, et al. Alopecia areata in families: association with the HLA locus. J Investig Dermatol Symp Proc. 1999;4:220-3.
6. 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;62:525-7.
7. Sundberg JP, Silva KA, Li R, et al. Adult-Onset Alopecia Areata Is a Complex Polygenic Trait in the C3H/HeJ Mouse Model. J Invest Dermatol 2004;123:294 -7.
8. Blaumeiser B, Goot Ineke van der, Fimmers R, et al. Familial aggregation of alopecia areata. J Am Acad Dermatol 2006;54:627-32.
9. Wang E, McElwee KJ. Etiopathogenesis of alopecia areata: Why do our patients get it? Dermatologic Therapy 2011;24:337-47.
10. Ito T, Tokura Y. The role of cytokines and chemokines in the T-cell-mediated autoimmune process in alopecia areata. Experimental Dermatology 2014;23:787-91.
11. Kalkan G, Karakus N, Baş Y, et al. The association between Interleukin (IL)-4 gene intron 3 VNTR polymorphism and alopecia areata (AA) in Turkish population. Gene 2013;527:565-9.
12. Uçmak D, Balcı G, Harman M. Evaluation of interleukin-2 and tumor necrosis factor-? levels in patients with lichen planus. Dicle Med J. 2012;39:6-8.
13. Sımpson RJ, Hammacher A, Smıth DK, Matthews JM, Ward LD. Interleukin-6: Structure-function relationships. Protein Science 1997;6929-55.
14. Hirano T. Interleukin 6 and its receptor: ten years later. Int Rev Immunol. 1998;16:249-84.
15. Wang HY, Zhang JJ, Zheng XY, et al. Association between IL- 6 Gene (- 174 & -572 G/C) Polymorphisms and Endometrial Adenocarcinoma Risk. Pathol. Oncol. Res. DOI 10.1007/s12253- 016-0073-6.
16. Belluco C, Olivieri F, Bonafe M, et al. -174G/C polymorphism of interleukin 6 gene promoter affects interleukin 6 serum level in patients with colorectal cancer. Clin Cancer Res. 2003;9:2173-6.
17. Bilgic O, Sivrikaya A, Unlu A, Altinyazar HC. Serum cytokine and chemokine profiles in patients with alopecia areata. J Dermatolog Treat. 2015;Oct 7:1-4.
18. 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- 72.
19. Cussigh A, Falleti E, Fabris C, et al. Interleukin 6 promoter polymorphisms influence the outcome of chronic hepatitis C. Immunogenetics 2011;63:33-41.
20. Pekiner FN, Aytugar E, Demirel GY, Borahan MO. Interleukin-2, interleukin-6 and T regulatory cells in peripheral blood of patients with Behc¸et's disease and recurrent aphthous ulcerations. J Oral Pathol Med. 2012;41:73-79.
21. Demirturk F, Ates O, Gunal O, et al. IL-6 gene promoter polymorphisms: genetic susceptibility to recurrent pregnancy loss. Bratisl Lek Listy 2014;115:479-82.
22. Al-Banna N, Raghupathy R, Albert MJ. Correlation of Proinflammatory and Anti-Inflammatory Cytokine Levels with Histopathological Changes in an Adult Mouse Lung Model of Campylobacter jejuni Infection. Clınıcal And Vaccıne Immunology, Dec. 2008;1780-7.
23. Bodemer C, Peuchmaur M, Fraitaig S, et al. Role of Cytotoxic T Cells in Chronic Alopecia Areata. J Invest Dermatol 2000;114:112-6.
24. Gregoriou S, Papafragkaki D, Kontochris GT, et al. Cytokines and Other Mediators in Alopecia Areata. Hindawi Publishing Corporation Mediators of Inflammation, 2010;5.
25. Brull DJ, Montgomery HE, Sanders J, et al. Interleukin-6 gene -174g > c and -572g > c promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery. Arterioscler Thromb Vasc Biol. 2001;21:1458-63.