Özgür CARTI, Yöntem YAMAN, Gülcihan ÖZEK, Hüseyin ONAY, Berna ATABAY, Canan VERGİN

TALASEMİ MAJÖR VE İNTERMEDİA HASTALARINDA HBS1L-MYB RS4895441 GEN POLİMORFİZMİNİN KLİNİĞE ETKİSİNİN DEĞERLENDİRİLMESİ

Giriş: Beta talasemiler en sık gözlenen otozomal resesif hastalıklardan biridir.Beta talasemilerde klinik özellikler son derece değişkendir.Hastalık ciddiyetini belirleyen ana faktörler, hastalığa neden olan mutasyonun kendisi (HBB gen mutasyonu) ve α/γ globulin zinciri üretme kapasitesidir. Bu çalışmada HbF düzeyindeki değişikliklerle ilişkili olduğu gösterilmiş 6q23.3 üzerindeki HBS1L-MYB interjenik bölgesindeki değişikliklerin kliniğe etkisinin araştırılması amaçlanmıştır. Gereç ve Yöntem: Talasemi majör ve intermedia tanısıyla izlenen 87 hasta çalışmaya alındı. Tanı yaşı, ilk transfüzyon yaşı, tanı dönemindeki kan sayımı verileri, HbF düzeyleri, splenektomi durumu, yıllık eritrosit transfüzyon miktarı (ml/kg/yıl), transfüzyonel demir yükü (mg/kg/gün), çalışma anındaki ferritin değerleri kaydedildi.HBS1L-MYB rs4895441 gen polimorfizmi PCR-RFLP yöntemi ile çalışıldı. Beta globin gen mutasyonu, αglobin gen mutasyonu, HBS1L-MYB rs4895441 gen polimorfizminin kliniğe etkisi ve talasemi intermedia kliniğini tahmin ettirici etkisi incelendi. Bulgular: HBS1L-MYB rs4895441 lokusunda en az bir G aleli taşıyan hastalarda ortalama tanı yaşı daha geç ve HbF düzeyleri daha yüksek saptandı. İyileştirici alellerin talasemi intermediayı tahmin ettirici etkisini değerlendirmek için yapılan lojistik regresyon analizinde HBS1L-MYB rs4895441polimorfizminin Tİ ile ilişkili olduğu saptandı. Sonuç: Gelecekteki tüm genom dizileme çalışmalarının, hastalık ciddiyetini değiştiren polimorfizmleri daha iyi tanımlaması muhtemel olsa da; bu çalışmanın sonuçları, HBS1L-MYB rs4895441 polimorfizminin daha geç tanı yaşı ve talasemi intermedia kliniğini öngörmede yardımcı olabileceğini göstermiştir.

THE EVALUATION OF THE CLINICAL EFFECT OF HBS1L-MYB RS4895441 GENE POLYMORPHISMS IN THALASSEMIA MAJOR AND INTERMEDIA PATIENTS

Introduction: Beta thalassemia is one of the most common autosomal recessive diseases. The clinical features of beta thalassemia are highly variable. The main factors that determine the severity of the disease are the mutation itself (HBB gene mutation) and the α/γ globulin chain production capacity. The aim of this study was to investigate the effect of changes in the HBS1L-MYB intergenic area on 6q23.3 which wasshown to be associated with changes in HbF level. Materials and Method: 87 thalassemia major and intermedia patients were enrolled in the study. Age of diagnosis, first transfusion age, blood count data at the time of diagnosis, HbF level, history of splenectomy, amount of erythrocyte transfusion (ml/kg/year), transfusional iron load (mg/kg/day), and ferritin level were examined. HBS1L-MYB rs4895441 gene polymorphism was studied by PCR-RFLP method. Beta globulin gene mutation, α globulin gene mutation, the effect of HBS1L-MYB rs4895441 gene polymorphism on the manifestation of the disease and the predicting the thalassemia intermedia manifestation were investigated. Results: Patients with at least one G allele in the HBS1L-MYB rs4895441 locus had a higher meanage of diagnosis and higher HbF levels. HBS1L-MYB rs4895441 polymorphism was found to be related to TI in the logistic regression analysis performed in order to assess the healing alleles in predicting thalassemia intermedia. Conclusion: Although it is likely that the future genome sequencing studies will beter describe the polymorphisms that alter these verity of disease, this study has shown that the HBS1L-MYB rs 4895441 polymorphism is related with higher age of diagnosis and may help in predicting thalassemia intermedia clinic.

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