Multiple Myeloma Hastalarında Sitokin Gen Polimorfizmleri ve Kromozom 13 Delesyonu

Abstract

Amaç: Multiple myeloma (MM), plazma hücrelerinin kemik iliği, lenfoid dokular ve çevre kanında birikmesidir. MM’de görülen en sık anomalilerden biri 13/13q delesyonudur ve yaklaşık %40-50 oranında görülür. Yapılan çalışmalar, hastaların çoğunda kromozom anomalisinin %80-90’ının monozomi 13 şeklinde iken %10-20’sinin bölgesel delesyonlar şeklinde olduğunu göstermiştir. Monozomi 13, sağkalımı belirleyen en önemli belirteçlerden biridir. Sitokinler, immün sistem hücrelerince salınan ve bu hücrelerin birçok fonksiyonunu düzenleyen proteinlerdir. Plazma hücresi, immünglobin üretiminde IL-1β, IL-6, IL-10 ve TNF-α gibi sitokinleri üretirler. Tek nükleotid polimorfizmleri de tek amino asit değişikliği ile sitokin fonksiyonunda ve üretiminde farklılıklar oluştururlar. Sitokinler ve kromozom 13 delesyonu (del13), MM hastalığı için önemli olan faktörlerden ikisidir. Biz de çalışmamızda MM ile del13 ve 10 sitokin (IL-1α, IL-1β, IL- 12, IFN-γ, TGF-β, TNF-α, IL-2, IL-4, IL-6, IL-10), 2 reseptör (IL-1R, IL-4Rα) ve 1 reseptör antagonistinin (IL-1RA) gen polimorfizmleri arasındaki ilişkiyi incelemeyi amaçladık. Gereç ve Yöntem: Çalışmaya multiple myeloma tanısı konmuş 38 hasta dahil edildi. Sitokin gen polimorfizm tiplemesi için PCR-SSP yöntemi kullanıldı (Protrans). Delesyon 13 için LSI D13S25 SO DNA probu kullanılarak FISH yöntemi uygulandı. Bulgular: Hastaların %40’ında del 13 saptandı. 13q delesyonu ve sitokin gen polimorfizmlerinin ayrı ayrı hasta yaşı, cinsiyeti, hastalık evresi ve β2-mikroglobulin seviyeleri ile istatistiksel analizi sonucu anlamlı bir değer gözlenmedi. LDH düzeyi ile TGF-β TG/TG haplotipi arasında istatistiksel anlamlılık saptandı (p:0.002). Sitokin polimorfizmleri ve del13 arasındaki ilişkiye bakıldığında anlamlı bir sonuç elde edilmedi (p>0.05). Sonuç: Sitokin polimorfizmi ve del13 varlığının hastalığın prognozu üzerine ayrı ayrı etkisi olsa da iki parametrenin birlikte prognoz üzerine etkisi saptanamadı.

Keywords

• Multiple myeloma
• Sitokin
• Polimorfizm
• Kromozom 13
• Delesyon

Cytokine Gene Polymorphisms and Chromosome 13 Deletion in Multiple Myeloma Patients

Abstract

Objective: Multiple myeloma (MM) is a clonal enlargement of plasma cells. The most common cytogenetic anomaly in MM is monosomy 13 and appears approximately 40%–50% in multiple myeloma. Studies have shown that in the majority of patients, 80%–90% of chromosomal anomalies are monosomy 13, and 10%–20% are regional deletions. Monosomy 13 is the most powerful predictor of survival in MM. Cytokines are proteins that regulate many functions of these cells and are secreted by cells of the immune system. Plasma cell stimulates angiogenesis by increasing the release of cytokines such as IL-1β, IL-6, and IL-10. Single nucleotide polymorphisms (SNP) of cytokine genes can affect their secretion rate or biological activity. Two of the important factors for MM disease are cytokines and chromosome 13 deletion (del13). We investigate chromosome 13 deletion and cytokine gene polymorphisms (IFN-γ, TGF-β, TNF-α, IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL-1R, IL-1Rα, IL-4Rα) in patients with MM. Materials and Methods: EDTA blood was collected from 38 patients with MM included in the study, and DNA was isolated. PCR-SSP method was used for cytokine gene polymorphism typing (Protrans). FISH method was applied using LSI D13S25 SO DNA probe for deletion 13. Results: 13q deletion was detected in 15 of the 38 of the patients. Statistical analysis of 13q deletion and cytokine gene polymorphisms was not statistically significant (p>0.05) by patient age, sex, disease stage, and β2-microglobulin levels. There is a statistical significance between level of LDH and TGF-β TG/TG haplotype (p=0.002). No significant results were obtained in the relationship between cytokine polymorphisms and del13 (p>0.05). Conclusion: Cytokines, which are associated with the function and viability of plasma cells, have a major role in the etiology and prognosis of the disease. Moreover, similar effects were observed with the 13q deletion. In our study, we did not find a statistical significance between cytokine gene polymorphisms and 13q deletion. Although both parameters independently have great importance on the effects of the disease, combining them together does not yield the same effect.

Keywords

• Cytokine
• Polymorphism
• Multiple Myeloma
• chromosome 13
• deletion

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