Özlem KAYIM YILDIZ, Ergün PINARBAŞI, Şeyda AKIN, Aslıhan Esra BİLDİRİCİ, Nilgün ÇEKİN

Multiple Skleroz ile FOXP3 geni promotor bölge mutasyonları arasındaki ilişki

Amaç: Bağışıklık sistemi bileşenlerinden biri olan düzenleyici T (Treg) hücreleri, özellikle multiple skleroz (MS) gibi otoimmün hastalıkların önlenmesinde oldukça etkilidir. Multiple skleroz (MS), santral sinir sisteminde immün hücre infiltrasyonu ve inflamasyonla karakterize kronik inflamatuar, otoimmün bir hastalıktır. Treg hücreleri otoimmünitenin kontrolünde önemli bir rol oynar. Treg’lerin gelişimi ve işlevi, transkripsiyon faktörü FOXP3’ün (Transkripsiyon Faktörü Forkhead Box P3) uygun ifadesine ve hareketine bağlıdır. Bu bağlamda çalışmamızın amacı, MS ve FOXP3 geni yaygın promotor bölge mutasyonlarından rs2232365 (-924 A/G) ve rs3761548 (-3279 A/C) arasındaki ilişkinin bir Türk popülasyonunda araştırılması olarak belirlenmiştir. Yöntem: Çalışma kapsamında 80 MS hastası ve 80 sağlıklı kontrol bireyinden alınan kan örnekleri kullanılmıştır. Foxp3 genotipleri PCR-RFLP yöntemi kullanılarak belirlenmiştir. Bulgular: Elde edilen sonuçlar istatistiksel olarak değerlendirildiğinde, MS ve FOXP3 rs3761548 polimorfizmi arasında anlamlı bir ilişki gözlenmiştir (p= 0.031). Bunun aksine araştırılan diğer polimorfizm, rs2232365, MS hastalarında hastalıkla ilişkili bulunmamıştır (p= 0.31). Sonuç: FOXP3 geni, bağışıklık hücrelerinin düzenlenmesinde en önemli genlerden biri olduğundan, MS hastalarında bu genin ekspresyonunun önemli olduğu sonucuna varılabilir. Bu SNP (Tek Nükleotit Polimorfizmi), genin promotor bölgesinde yer aldığından FOXP3 proteinin ekspresyon seviyesini etkileyebilir.

Association between Multiple Sclerosis and FOXP3 Gene promoter region mutations

Regulatory T-Cells (Treg Cells), as one of the immune system components, have been highly effective in theautoimmune diseases prevention, particularly multiple sclerosis (MS). MS is a chronic inflammatory and autoimmunedisease characterized by immune infiltration and inflammation in the central nervous system. Regulatory T (Treg) cellsplay an important role in the control of autoimmunity. Expression and action of the transcription factor FOXP3 controlsthe development and function of Treg cell. The aim of this study was to investigate the association between MS andFOXP3 gene promoter region polymorphisms rs2232365 (-924A/G) and rs3761548 (-3279A/C) in a Turkishpopulation. In this case-control study we investigated these polymorphisms in 80 MS patients and 80 healthy controlsusing PCR-RFLP methods.Results of our study showed that while there is significant correlation between MS and FOXP3 rs3761548polymorphism (p=0.031), FOXP3 rs2232365 polymorphism, has not been found to be associated with the disease(p=0.31). As FOXP3 gene is one of the most important genes in the regulation of the immune cells, it may beconcluded that the expression of this gene is important in MS patients. As this SNP is located in the promoter region ofthe gene, it may affect the expression level of FOXP3 protein.

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