H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
Sci Rep. 2019 Feb 14;9(1):2041. doi: 10.1038/s41598-019-38823-0.
β-Thalassemia is a widespread autosomal recessive blood disorder found in most parts of the world. Fetal hemoglobin (HbF), a form of hemoglobin is found in infants, replaced by adult hemoglobin (HbA) after birth. Hydroxyurea (HU) is one of the most effective HbF inducer used for the treatment of anemic diseases. We aimed to improve the understanding of HU therapy in β-thalassemia by metabonomics approach using H NMR spectroscopy. This study includes 40 cases of β-thalassemia before and after HU therapy along with 40 healthy as controls. Carr-Purcell-Meiboom-Gill (CPMG) sequence was used to identify forty-one putative metabolites. Generation of models like partial least square discriminant analysis (PLS-DA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA) based on different metabolites including lipids, amino acids, glucose, fucose, isobutyrate, and glycerol revealed satisfactory outcomes with 85.2% and 91.1% classification rates, respectively. The concentration of these metabolites was altered in β-thalassemia samples. However, after HU treatment metabolic profile of same patients showed closeness towards healthy. Deviant metabolic pathways counting lipoprotein changes, glycolysis, TCA cycle, fatty acid and choline metabolisms were identified as having significant differences among study groups. Findings of this study may open a better way to monitor HU treatment effectiveness in β-thalassemia patients, as the results suggested that metabolic profile of β-thalassemia patients shows similarity towards normal profile after this therapy.
β-地中海贫血是一种广泛存在的常染色体隐性遗传性血液疾病，在世界大多数地区都有发现。胎儿血红蛋白（HbF）是婴儿体内存在的一种血红蛋白形式，出生后被成人血红蛋白（HbA）取代。羟基脲（HU）是治疗贫血疾病最有效的 HbF 诱导剂之一。我们旨在通过使用 H NMR 光谱的代谢组学方法来提高对 HU 治疗β-地中海贫血的理解。这项研究包括 40 例接受 HU 治疗前后的β-地中海贫血患者和 40 例健康对照者。Carr-Purcell-Meiboom-Gill (CPMG) 序列用于鉴定 41 种可能的代谢物。基于不同的代谢物，如脂质、氨基酸、葡萄糖、岩藻糖、异丁酸和甘油，生成偏最小二乘判别分析（PLS-DA）和正交偏最小二乘判别分析（OPLS-DA）模型，分别得到 85.2%和 91.1%的分类率，结果令人满意。这些代谢物的浓度在β-地中海贫血样本中发生了改变。然而，在 HU 治疗后，相同患者的代谢谱显示出与健康人群的接近程度。脂蛋白变化、糖酵解、三羧酸循环、脂肪酸和胆碱代谢等异常代谢途径被确定为研究组之间具有显著差异的途径。本研究的结果可能为监测β-地中海贫血患者 HU 治疗效果提供更好的方法，因为结果表明，β-地中海贫血患者的代谢谱在接受这种治疗后显示出与正常谱相似的趋势。
