Correlation of BACH1 and Hemoglobin E/Beta-Thalassemia Globin ExpressionTze Yan Lee1, Logeswaran Muniandy1, Lai Kuan Teh1, Maha Abdullah1, Elizabeth George2, Jameela Sathar3, Mei I Lai21Universiti Putra Malaysia Faculty of Medicine and Health Sciences, Department of Pathology, Serdang, Malaysia
2Universiti Putra Malaysia Faculty of Medicine and Health Sciences, Department of Pathology, Genetic and Regenerative Medicine Research Centre, Serdang, Malaysia
3Ampang Hospital, Clinic of Hematology, Selangor, Malaysia
INTRODUCTION: The diverse clinical phenotype of hemoglobin E (HbE)/β- thalassemia has not only confounded clinicians in matters of patient management but has also led scientists to investigate the complex mechanisms involved in maintaining the delicate red cell environment where, even with apparent similarities of α- and β-globin genotypes, the phenotype tells a different story. The BTB and CNC homology 1 (BACH1) protein is known to regulate α- and β-globin gene transcriptions during the terminal differentiation of erythroid cells. With the mutations involved in HbE/β-thalassemia disorder, we studied the role of BACH1 in compensating for the globin chain imbalance, albeit for fine-tuning purposes.
METHODS: A total of 47 HbE/β-thalassemia samples were analyzed using real-time quantitative polymerase chain reaction and correlated with age, sex, red blood cell parameters, globin gene expressions, and some clinical data.
RESULTS: The BACH1 expression among the β-thalassemia intermedia patients varied by up to 2-log differences and was positively correlated to age; α -, β-, and γ-globin gene expression level; and heme oxygenase 1 protein. BACH1 was also negatively correlated to reticulocyte level and had a significant correlation with splenectomy.
DISCUSSION AND CONCLUSION: This study indicates that the expression of BACH1 could be elevated as a compensatory mechanism to decrease the globin chain imbalance as well as to reduce the oxidative stress found in HbE/β-thalassemia.
Keywords: BACH1, Gene expression, Hemoglobin E/β, -thalassemia, Oxidative stress, Red blood cell parameters
BACH1 ve Hemoglobin E/Beta-Talasemi Globin Sunumu KorelasyonuTze Yan Lee1, Logeswaran Muniandy1, Lai Kuan Teh1, Maha Abdullah1, Elizabeth George2, Jameela Sathar3, Mei I Lai21Universiti Putra Malaysia Faculty of Medicine and Health Sciences, Department of Pathology, Serdang, Malaysia
2Universiti Putra Malaysia Faculty of Medicine and Health Sciences, Department of Pathology, Genetic and Regenerative Medicine Research Centre, Serdang, Malaysia
3Ampang Hospital, Clinic of Hematology, Selangor, Malaysia
GİRİŞ ve AMAÇ: Hemoglobin E (HbE)/β-talaseminin çeşitli klinik fenotipleri klinisyenlerin hasta yönetimi esnasında zihinlerini karıştırmakla kalmamış, α- ve β-globin genotiplerinde bariz benzerlikler varken fenotiplerde farklılıklar bulunduğundan bilim insanlarının hassas eritrosit çevrenin muhafaza edilmesinde yer alan karmaşık mekanizmaları incelemelerine de ön ayak olmuştur. BTB ve CNC homoloji 1 (BACH1) proteininin eritroid hücrelerin son farklılaşması sırasında α- and β-globin gen transkripsiyonlarını ayarladığı bilinmektedir. HbE/β-talasemi hastalığındaki mutasyonlar ile her ne kadar ince ayar amaçlı ise de BACH1’in globin zincir dengesizliğini kompanse etmedeki rolünü inceledik.
YÖNTEM ve GEREÇLER: Toplam 47 HbE/β-talasemi örneği gerçek zamanlı kantitatif polimeraz zincir reaksiyonu ile incelendi ve yaş, cinsiyet, eritrosit değişkenleri, globin gen sunumları ve bazı klinik veriler ile korele edildi.
BULGULAR: β-talasemi intermedia hastalarındaki BACH1 sunumu 2-log’a kadar farklılık göstermekteydi ve yaş; α-, β- ve γ-globin gen sunum düzeyleri; ve hem oksijenaz 1 proteini ile pozitif korelasyonu vardı. Ayrıca BACH1’in retikülosit düzeyi ile negatif korelasyonu vardı ve splenektomi ile anlamlı korelasyonu bulunmaktaydı.
TARTIŞMA ve SONUÇ: Bu çalışma hem HbE/β-talasemide bulunan oksidatif stresi hem de globin zincir dengesizliğini azaltmak için BACH1 sunumunun kompansasyon mekanizması olarak artabileceğini göstermiştir.
Anahtar Kelimeler: BACH1, Gen sunumu, Hemoglobin E/β, -talasemi, Oksidatif stres, Eritrosit değişkenleri
Tze Yan Lee, Logeswaran Muniandy, Lai Kuan Teh, Maha Abdullah, Elizabeth George, Jameela Sathar, Mei I Lai. Correlation of BACH1 and Hemoglobin E/Beta-Thalassemia Globin Expression. Turk J Hematol. 2016; 33(1): 15-20
Corresponding Author: Mei I Lai, Malaysia |
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