Abstract:
BACKGROUND:The phenotypic severity of β-thalassemia is highly modulated by three genetic modifiers: β-globin (HBB) mutations, co-inheritance of α-thalassemia and polymorphisms in the genes associated with fetal haemoglobin (HbF) production. This study was aimed to evaluate the effect of HbF related polymorphisms mainly in the HBB cluster, BCL11A (B-cell CLL/lymphoma 11A) and HBS1L-MYB (HBS1-like translational GTPase-MYB protooncogene, transcription factor) with regards to clinical severity. METHODS:A total of 149 patients were included in the study. HBA and HBB mutations were characterised using multiplex PCR, Sanger sequencing and multiplex ligationdependent probe amplification. In addition, 35 HbF polymorphisms were genotyped using mass spectrometry and PCR-restriction fragment length polymorphism (PCRRFLP). The genotype-phenotype association was analysed using SPSS version 22. RESULTS:Twenty-one HBB mutations were identified in the study population. Patients with HBB mutations had heterogeneous phenotypic severity due to the presence of other secondary modifiers. Co-inheritance of α-thalassemia (n = 12) alleviated disease severity of β-thalassemia. In addition, three polymorphisms (HBS1LMYB, rs4895441 [P = 0.008, odds ratio (OR) = 0.38 (0.18, 0.78)], rs9376092 [P = 0.030, OR = 0.36 (0.14, 0.90)]; and olfactory receptor [OR51B2] rs6578605 [P = 0.018, OR = 0.52 (0.31, 0.89)]) were associated with phenotypic severity. Secondary analysis of the association between single-nucleotide polymorphisms with HbF levels revealed three nominally significant SNPs: rs6934903, rs9376095 and rs9494149 in HBS1L-MYB. CONCLUSION:This study revealed 3 types of HbF polymorphisms that play an important role in ameliorating disease severity of β-thalassemia patients which may be useful as a predictive marker in clinical management.
journal_name
Curr Mol Medjournal_title
Current molecular medicineauthors
Razak SAA,Murad NAA,Masra F,Chong DLS,Abdullah N,Jalil N,Alauddin H,Sabudin RZAR,Ithnin A,Khai LC,Aziz NA,Muda Z,Ibrahim H,Latiff ZAdoi
10.2174/1566524018666181004121604subject
Has Abstractpub_date
2018-01-01 00:00:00pages
295-305issue
5eissn
1566-5240issn
1875-5666pii
CMM-EPUB-93432journal_volume
18pub_type
临床试验,杂志文章abstract::There has been prolonged and significant interest in manipulating the genome for a wide range of applications in biomedical research and medicine. An existing challenge in realizing this potential has been the inability to precisely edit specific DNA sequences. Past efforts to generate targeted double stranded DNA cle...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524016666160316150847
更新日期:2016-01-01 00:00:00
abstract::Glutathione transferase Pi (GST-pi, GSTP) is known to strongly affect human susceptibility to several cancers, asthma and neurodegenerative disorders. As with other glutathione transferases, it catalyses the addition of reduced glutathione to electrophilic species, and it is important in metabolite detoxification. It ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652411794859278
更新日期:2011-03-01 00:00:00
abstract::Salmonella infections are a serious public health problem in developing countries and represent a constant concern for the food industry. The severity and the outcome of a systemic Salmonella infection depends on the "virulence" of the bacteria, on the infectious dose as well as on the genetic makeup and immunological...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524023362492
更新日期:2002-06-01 00:00:00
abstract::Deregulation of the PI3K pathway is common in human cancer. The basic players in this pathway are the kinases PI3K and AKT and the phosphatase PTEN. This review will summarize some of the key animal models that have helped us understand this signaling network and its contribution to tumorigenesis. Recently, great adva...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652409788488766
更新日期:2009-06-01 00:00:00
abstract::Plaque disruption and subsequent thrombus formation play a critical role in the clinical manifestations of atherothrombosis. Vulnerable lesions are characterized by the existence of core rich in lipid, macrophages and tissue factor (TF). Plaque disruption facilitates the interaction between flowing blood with the inne...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652406778018707
更新日期:2006-08-01 00:00:00
abstract::The view that mitochondrial electron transport is the only site of aerobic respiration and the primary bioenergetic pathway in mammalian cells is well established in the literature. Although this paradigm is widely accepted for most tissues, the situation is less clear for proliferating cells. Increasing evidence indi...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652406779010777
更新日期:2006-12-01 00:00:00
abstract::Cholesterol is a chameleon bio-molecule in cellular multiplex. It acts as a prelate in almost every cellular compartment with its site specific characteristics viz. regulation of structural veracity and scaffold fluidity of bio-membranes, insulation of electrical transmission in nerves, controlling of genes by making ...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524020666200413112030
更新日期:2020-01-01 00:00:00
abstract::The prevalence of insulin resistance and diabetes mellitus is rising globally in epidemic proportions. Diabetes and its complications contribute to significant morbidity and mortality. Increase in sedentary lifestyle and consumption of more energy-dense diet increased the incidence of obesity which is a significant ri...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524020666200812221527
更新日期:2020-08-12 00:00:00
abstract::Bitter gourd (Momordica charantia, BG) is both a nutritious and healthy food with a distinctive bitter flavor, and it is also widely exploited in folklore medicine. This review focuses on the efficacies and molecular mechanisms of BG-induced anti-diabetic, anti-HIV, and antitumor activities contributed by over twenty ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652411795976583
更新日期:2011-07-01 00:00:00
abstract::Ca2+ ions are involved in the regulation of many diverse functions in animal and plant cells, e.g. muscle contraction, secretion of neurotransmitters, hormones and enzymes, fertilization of oocytes, and lymphocyte activation and proliferation. The intracellular Ca2+ concentration can be increased by different molecula...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524024605707
更新日期:2002-05-01 00:00:00
abstract::Evidence shows that artificially lowering body and brain temperature can significantly reduce the deleterious effects of brain injury in both newborns and adults. Although the benefits of therapeutic hypothermia have long been known and applied clinically, the underlying molecular mechanisms have yet to be elucidated....
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652412803833517
更新日期:2012-12-01 00:00:00
abstract::Extracellular matrices (ECMs) are dynamic structures that provide cells not only with a structural support but, importantly, exhibit significant functional roles in the control of key cellular events such as adhesion, migration, proliferation, differentiation, and survival. In tumors, matrix effectors such as proteogl...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652412802480943
更新日期:2012-09-01 00:00:00
abstract::Human induced pluripotent stem cells (hiPSCs) have great potential as a robust source of progenitors for regenerative medicine. The novel technology also enables the derivation of patient-specific cells for applications to personalized medicine, such as for personal drug screening and toxicology. However, the biologic...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524011313050010
更新日期:2013-06-01 00:00:00
abstract::Glycogen is a branched polymer of glucose which serves as a reservoir of glucose units. The two largest deposits in mammals are in the liver and skeletal muscle but many cells are capable synthesizing glycogen. Its accumulation and utilization are under elaborate controls involving primarily covalent phosphorylation a...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524024605761
更新日期:2002-03-01 00:00:00
abstract:BACKGROUND:Osteoporosis is a systemic skeletal disease characterized by low bone mineral density. Vitamin D metabolism may play a pivotal role in its pathophysiology. OBJECTIVES:To determine the association between Vitamin D receptor gene polymorphisms and bone density, as well as its relation to biochemical markers o...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190409122155
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Oxidative stress and chronic hyperglycemia are two major side effects of type 2 diabetes affecting all cell types including mesenchymal stem cells (MSCs). As a cell therapy choice, understanding the behavior of MSCs will provide crucial information for efficient treatment. METHODS:Placental mesenchymal stem...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190722115842
更新日期:2019-01-01 00:00:00
abstract::Type 1 diabetes (T1D) is an organ-specific autoimmune disease resulting from the specific destruction of insulin-producing pancreatic beta-cells, culminating in a state of hypoinsulinemia and hyperglycemia. Pathogenesis of T1D comprises complex series of events from the initial sensitization of antigen-presenting cell...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652409787314471
更新日期:2009-02-01 00:00:00
abstract::Many potential HIV vaccine strategies are being explored in both animal model and human settings. The success of any vaccine relies on relevant antigenic determinants being presented to the immune system for the activation of broad and long-lasting immunity. Effective immunity against HIV infection will likely require...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524033479870
更新日期:2003-05-01 00:00:00
abstract:BACKGROUND:Obesity is a chronic condition associated with poorer cognitive functioning. Wisconsin Card Sorting Test (WCST) is a useful tool for evaluating executive functions. In this study, we assessed the association between dopaminergic gene polymorphisms: DAT1 (SLC6A3), COMTVal158Met, DRD4 (48-bp variable number of...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190424143653
更新日期:2019-01-01 00:00:00
abstract::Germline mutations in the VHL tumour suppressor gene may cause a variety of phenotypes including von Hippel-Lindau (VHL) disease, familial phaeochromocytoma and inherited polycythaemia. VHL disease is a multisystem familial cancer syndrome and is the commonest cause of familial renal cell carcinoma (RCC). VHL disease ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524043359827
更新日期:2004-12-01 00:00:00
abstract:BACKGROUND:In vertebrates, cilium is crucial for Hedgehog signaling transduction. Forkhead box transcriptional factor FoxF1 is reported to be associated with Sonic Hedgehog (Shh) signaling in many cases. However, the role of FoxF1 in cilium remains unknown. Here, we showed an essential role of FoxF1 in the regulation o...
journal_title:Current molecular medicine
pub_type: 信件
doi:10.2174/1566524019666190405115420
更新日期:2019-01-01 00:00:00
abstract::The central role of glutamate receptors in mediating excitotoxic neuronal death in stroke, epilepsy and trauma has been well established. Glutamate is the major excitatory amino acid transmitter within the CNS and it's signaling is mediated by a number of postsynaptic ionotropic and metabotropic receptors. Although ca...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524043479202
更新日期:2004-03-01 00:00:00
abstract:OBJECTIVES:Celastrol, a quinone methide triterpenoid, could induce apoptosis in pancreatic cancer cells. The purpose of this study is to determine whether there is protective autophagy after celastrol treatment in pancreatic cancer cells and the synergistic effects of celastrol and 3-MA in vitro and in vivo. METHODS:T...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524014666140414211223
更新日期:2014-05-01 00:00:00
abstract::Phospholipases A2 (PLA2s) represent a growing family of enzymes that catalyze the hydrolysis of phospholipids at the sn-2 position leading to the generation of free fatty acids and lysophospholipids. Mammalian PLA2s are divided into two major classes according to their molecular mass and location: intracellular PLA2 a...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524013363258
更新日期:2001-12-01 00:00:00
abstract::Type 2 diabetes carries a 2-6-fold increased risk of cardiovascular disease (CVD) and death. Indeed, the risk of major cardiovascular events in Type 2 diabetic patients without history of coronary heart disease (CHD) is equivalent to that observed in non-diabetic subjects with CHD. However, atherosclerosis may also pr...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524053766095
更新日期:2005-05-01 00:00:00
abstract:OBJECTIVE:This study aims to investigate the effect of morphine with naloxone on intestinal peristalsis and the number of interstitial cells of Cajal (ICC) in colon tissues of rabbits. METHODS:Thirty rabbits were randomly divided into five groups (n=6, each group): saline control group (NS group), low concentration of...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666191023112837
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Inclusion of anticancer drugs into biocompatible nanoparticulate carriers decreases the general toxicity and improves the efficacy of clinical treatments due to the reduction of soluble circulating free drug. METHODS:In addition, removal of emerging drug contaminants from wastewaters is a necessity that sho...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524021666210111104428
更新日期:2021-01-10 00:00:00
abstract::Hypoxia or oxygen deficiency is a salient feature of solid tumors. Hypoxic tumors are often resistant to conventional cancer therapies, and tumor hypoxia correlates with advanced stages of malignancy. Hypoxic tumors appear to be poorly differentiated. Increasing evidence suggests that hypoxia has the potential to inhi...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652409788167113
更新日期:2009-05-01 00:00:00
abstract::The mitochondrial 18 kDa Translocator Protein (TSPO) was first detected by its capability to bind benzodiazepines in peripheral tissues and later also in glial cells in the brain, hence its previous most common name peripheral benzodiazepine receptor (PBR). TSPO has been implicated in various functions, including apop...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524011207040398
更新日期:2012-05-01 00:00:00
abstract::A critical challenge faced by clinical nephrologists today is the escalating number of patients developing end stage renal disease, a major proportion of which is attributed to diabetic nephropathy (DN). The need for new measures to prevent and treat this disease cannot be overemphasized. To this end, modern genetic a...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524054553504
更新日期:2005-08-01 00:00:00