Eylem PARLAK, Aydan AKDENİZ, Nurcan ARAS

TNF-α (rs1800629) ve IKZF1 (rs4132601) gen polimorfizmlerinin Hodgkin lenfoma patogenezindeki rolü

Amaç: Tümör nekroz faktör-alfa (TNF-α), nekroz veya apoptoza yol açan çeşitli sinyal yolaklarında, inflamatuvar ve otoimmün hastalıkların patogenezinde rol oynamaktadır. TNF-α genindeki rs1800629 polimorfizmi G>A değişimi yaparak genin ifade seviyelerini etkiler. TNF-α -308G alleli ile karşılaştırıldığında, A alleli daha yüksek transkripsiyonel aktiviteye sahiptir. IKZF1 geni ise, hücre döngüsünün ilerlemesini ve hücre sağkalımını kontrol eden genlerin ekspresyonunu düzenleyen transkripsiyon faktörü IKAROS'u kodlamaktadır. IKZF1 geni, kromatinin yeniden şekillenmesi ile ilişkili çinko parmak DNA bağlayıcı proteinler ailesindendir. Bu protein lenfosit diferansiasyonunun da düzenleyicisidir. IKZF1 genindeki rs4132601 polimorfizminin T/G değişimi yaparak genin ekspresyon seviyesini etkilediği ve otoimmün hastalıklar ve lenfoma ile ilişkili olduğu bulunmuştur. TNF-α ile IKZF1 gen polimorfizmlerinin Hodgkin lenfoma için bir risk faktörü olup olmadığını değerlendirmeyi amaçladık. Yöntem: Hodgkin lenfoma tanısı olan hasta grubu ile malignitesi olmayan kontrol grubu hastalarda TNF-α ve IKZF1gen polimorfizmleri gerçek zamanlı polimeraz zincir reaksiyon (Rt-PCR) yöntemi ile araştırılmıştır. Elde edilen veriler SPSS paket programında analiz edilmiştir. Bulgular: TNF-α (rs1800629) genindeki polimorfizmde, gruplara göre TNF-α (rs1800629) genotip ve allel dağılımlarının farklılık göstermediği saptanmıştır (p>0.05). Gruplara göre TNF-α (rs4132601) genotipler arasında farklılık göstermediği anacak allel dağılımlarının farklılık gösterdiği saptanmıştır (p=0,087), ve hasta grubunda kontrol grubuna kıyasla G alleli T alleline göre 2,34 kat daha fazla tespit edilmiştir. Sonuç: Bulgularımız, IKZF1 (rs4132601) geninde G allelinin Hodgkin lenfoma için bir risk faktörü olabileceğini göstermektedir.

Anahtar Kelimeler:

Hodgkin lenfoma, Gen polimorfizmi, TNF-α (rs1800629), IKZF1 (rs4132601)

The role of TNF-α (rs1800629) ve IKZF1 (rs4132601) gen polimorphisms in pathogenesis of Hodgkin’s lymphoma

Aim: Tumor necrosis factor-alpha (TNF-α) plays a role in various signaling pathways leading to necrosis or apoptosis and in the pathogenesis of inflammatory and autoimmune diseases. The rs1800629 polymorphism in the TNF-α gene affects the expression levels of the gene by making a G>A exchange. The IKZF1 gene encodes the transcription factor IKAROS, which regulates the expression of genes that control cell cycle permanence and cell survival. The IKZF1 gene is in the family of zinc finger DNA-binding proteins associated with chromatin remodeling. This protein is also a regulator of lymphocyte differentiation. The rs4132601 polymorphism in the IKZF1 gene affects the expression level of the gene by making a T/G exchange, and have been found to be associated with autoimmune diseases and lymphoma. We aimed to explore TNF-α and IKZF1 gene polymorphisms in patients with Hodgkin lymphoma and investigate whether we could identify them as risk factors. Method: TNF-α and IKZF1 gene polymorphisms were analyzed in patient group diagnosed with Hodgkin lymphoma and the control group without malignancy. The results were evaluated with the Chi-Square test. Data were analyzed in the Statistical Package for the Social Sciences (SPSS) program. Results: TNF-α (rs1800629) genotype and allele distributions did not differ between two groups (p>0.05). IKZF1 (rs4132601)allele distributions differed between the groups (p=0.087), and G allele was detected 2.34 times more than T allele in the patient group compared to the control group. Conclusion: Our results indicate that G allele in IKZF1 (rs4132601) gene may be a risk factor for Hodgkin lymphoma.

Keywords:

Hodgkin lymphoma, gene polimorphism, TNF-α (rs1800629), IKZF1 (rs4132601),

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