Genetic Modifiers of Fetal Haemoglobin (HbF) and Phenotypic Severity in β-Thalassemia Patients.

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 Med

authors

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 ZA

doi

10.2174/1566524018666181004121604

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

295-305

issue

5

eissn

1566-5240

issn

1875-5666

pii

CMM-EPUB-93432

journal_volume

18

pub_type

临床试验,杂志文章
  • A review of studies on targeting interleukin 4 receptor for central nervous system malignancy.

    abstract::Despite advances in biomedical sciences, the prognosis of patients with brain tumors remains poor. Effective treatment is lacking for these central nervous system (CNS) cancers. Targeted immunotoxins are a new class of therapeutic approaches that have emerged for the treatment of human cancers. In this approach, tumor...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652409788970661

    authors: Puri S,Puri S,Mahapatra AK,Hussain E,Sarkar C,Sinha S,Joshi BH

    更新日期:2009-08-01 00:00:00

  • Protein serine/threonine phosphotase-1 is essential in governing normal development of vertebrate eye.

    abstract::Protein serine/threonine phosphatase-1 (PP-1) is one of the key enzymes responsible for dephosphorylation in vertebrates. Protein dephosphorylation via PP-1 is implicated in many different biological processes including gene expression, cell cycle control, transformation, neuronal transmission, apoptosis, autophage an...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/156652412803833535

    authors: Liu WB,Yan Q,Liu FY,Tang XC,Chen HG,Liu J,Nie L,Zhang XW,Ji WK,Hu XH,Hu WF,Woodward Z,Wu KL,Wu MX,Liu XL,Luo LX,Yu MB,Liu YZ,Liu SJ,Li DW

    更新日期:2012-12-01 00:00:00

  • Specific Roles of NMDA Receptor Subunits in Mental Disorders.

    abstract::N-methyl-D-aspartate (NMDA) receptor plays important roles in learning and memory. NMDA receptors are a tetramer that consists of two glycine-binding subunits GluN1, two glutamate-binding subunits (i.e., GluN2A, GluN2B, GluN2C, and GluN2D), a combination of a GluN2 subunit and glycine-binding GluN3 subunit (i.e., GluN...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524015666150330142807

    authors: Yamamoto H,Hagino Y,Kasai S,Ikeda K

    更新日期:2015-01-01 00:00:00

  • Molecular mechanisms of resistance to antiviral therapy in patients with chronic hepatitis B.

    abstract::Similar to the human immunodeficiency virus (HIV), the hepatitis B virus (HBV) replicates via reverse transcription, in this case, within infected hepatocytes. Substantial advances have been achieved in the past ten years in developing and utilizing nucleoside/nucleotide analog drugs to inhibit HBV replication. Most a...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652407780059159

    authors: Yuan HJ,Lee WM

    更新日期:2007-03-01 00:00:00

  • Membrane Fusion Mediated Targeted Cytosolic Drug Delivery Through scFv Engineered Sendai Viral Envelopes.

    abstract::Antibody targeted cytoplasmic delivery of drugs is difficult to achieve as antigen-antibody interaction results in the payload being directed to the endosomal compartment. However, Sendai viral envelopes can bring about cytoplasmic delivery due to F-protein mediated membrane fusion. In this study we have generated and...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524015666150505155949

    authors: Kumar M,Mani P,Pratheesh P,Chandra S,Jeyakkodi M,Chattopadhyay P,Sarkar DP,Sinha S

    更新日期:2015-01-01 00:00:00

  • Mesenchymal stem cells regulate cytoskeletal dynamics and promote cancer cell invasion through low dose nitric oxide.

    abstract::Bone marrow-derived mesenchymal stem cells (BMSCs) can be recruited to tumor sites and integrate into the stroma of tumors. When co-cultured with BMSCs, otherwise weakly metastatic nasopharyngeal carcinoma cells (NPC) showed improved metastatic ability. BMSCs in the tumor environment displayed the characteristics of m...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524014666140724102301

    authors: Zhang L,Sun J,Liu Z,Dai Y,Luo Z,Jiang X,Li Z,Li Y,Cao P,Zhou Y,Zeng Z,Tang A,Li X,Li X,Xiang J,Li G

    更新日期:2014-01-01 00:00:00

  • Cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP): novel regulators of Ca2+-signaling and cell function.

    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

    authors: Guse AH

    更新日期:2002-05-01 00:00:00

  • The protein-protein interaction-mediated inactivation of PTEN.

    abstract::PTEN (Phosphatase and Tensin homologue deleted on chromosome 10, 10q23.3) is the dominant phosphatase responsible for the dephosphorylation of the 3-position phosphate from the inositol ring of phosphatidylinositol 3,4,5 triphosphate (PIP3), and thereby directly antagonizes the actions mediated by Phosphatidylinositol...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524013666131118100542

    authors: De Melo J,He L,Tang D

    更新日期:2014-01-01 00:00:00

  • LTP, memory and structural plasticity.

    abstract::Our current understanding of the mechanisms of information processing and storage in the brain, based on the concept proposed more than fifty years ago by D. Hebb, is that a key role is played by changes in synaptic efficacy induced by coincident pre- and postsynaptic activity. Decades of studies of the properties of ...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524023362041

    authors: Muller D,Nikonenko I,Jourdain P,Alberi S

    更新日期:2002-11-01 00:00:00

  • The study of HLA class II and autoimmune diabetes.

    abstract::Many autoimmune diseases have genetic associations with the Major Histocompatibility Complex (MHC) class II loci. Susceptibility to Type 1 diabetes mellitus (TIDM) is particularly associated with Human Leucocyte Antigen (HLA) DR3, 4 and associated DQ2, 8 alleles and this is well documented in genetic association studi...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524033361591

    authors: Wong FS,Wen L

    更新日期:2003-02-01 00:00:00

  • Entosis and Related Forms of Cell Death within Cells.

    abstract::By eliminating the unneeded or mutant cells, programmed cell death actively participates in a wide range of biological processes from embryonic development to homeostasis maintenance in adult. Continuing efforts have identified multiple cell death pathways, with apoptosis, necrosis and autophage the mostly studied. Re...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524015666151026100339

    authors: Wang Y,Wang XD

    更新日期:2015-01-01 00:00:00

  • Skin aging: a role for telomerase and telomere dynamics?

    abstract::Skin is a complex tissue composed of two very different compartments -- the continuously renewing epidermis made up mostly by keratinocytes and the underlying matrix-rich dermis with the resting fibroblasts as its major cellular components. Both compartments are tightly interconnected and a paracrine mutual interactio...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524053586644

    authors: Boukamp P

    更新日期:2005-03-01 00:00:00

  • Potential Therapeutic Applications of MDA-9/Syntenin-NF-κB-RKIP Loop in Human Liver Carcinoma.

    abstract:BACKGROUND:Overexpression of MDA-9/Syntenin occurs in multiple human cancer cell lines and is associated with higher grade of tumor classification, invasiveness and metastasis. In some cases, its role in cancer biology depends on relationships between MDA-9/Syntenin and NF-κB. OBJECTIVE:This study aims to analyze the ...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524019666190104105043

    authors: Notarbartolo M,Labbozzetta M,Pojero F,D'Alessandro N,Poma P

    更新日期:2018-01-01 00:00:00

  • Studying Adsorption and Cellular Toxicity of Boron Nitride Nanostructure versus Melphalan Anti-ovarian Cancer Drug.

    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

    authors: Fu M,Tayebee R,Saberi S,Nourbakhsh N,Esmaeili E,Maleki B,Vatanpour HR

    更新日期:2021-01-10 00:00:00

  • Induced pluripotent stem cells (iPSCs) derived from different cell sources and their potential for regenerative and personalized medicine.

    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

    authors: Shtrichman R,Germanguz I,Itskovitz-Eldor J

    更新日期:2013-06-01 00:00:00

  • Effects of Morphine on Interstitial Cells of Cajal in Rabbit Colon and Small Intestinal Transit: An Experimental Study.

    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

    authors: Yang H,Jin XJ,Luo H,Li YH

    更新日期:2020-01-01 00:00:00

  • The role of transcriptome analysis in pre-clinical toxicology.

    abstract::A major benefit of the genomics revolution in biomedical research has been the establishment of transcriptome analysis as an enabling technology in the drug development process. Nowhere in the realm of drug development has the expectation of the impact of transcriptome analysis been greater than in the area of pre-cli...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524053152825

    authors: Searfoss GH,Ryan TP,Jolly RA

    更新日期:2005-02-01 00:00:00

  • cAMP signalling in the kinetoplastid protozoa.

    abstract::Several species of kinetoplastid protozoa cause major human infectious diseases. Trypanosoma cruzi is responsible for the fatal Chagas disease in large parts of South America, the various species of Leishmania cause a number of different human diseases with millions of patients world-wide, and the African trypanosome ...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524043360113

    authors: Seebeck T,Schaub R,Johner A

    更新日期:2004-09-01 00:00:00

  • The Impact of CRISPR/Cas9-Based Genomic Engineering on Biomedical Research and Medicine.

    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

    authors: Go DE,Stottmann RW

    更新日期:2016-01-01 00:00:00

  • Pathogenesis of central nervous system tuberculosis.

    abstract::Central Nervous System (CNS) tuberculosis is a serious, often fatal form of tuberculosis, predominantly affecting young children. HIV co-infection and drug resistant strains of Mycobacterium tuberculosis are making the diagnosis and treatment of CNS tuberculosis more complicated. Current concepts about the pathogenesi...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652409787581655

    authors: Be NA,Kim KS,Bishai WR,Jain SK

    更新日期:2009-03-01 00:00:00

  • RAN GTPase as a target for cancer therapy: Ran binding proteins.

    abstract::The identification of a relevant effector of Ran GTPase (Ran) signaling and its pathways could provide a novel approach to cancer therapeutics. With recent research highlighting the significant relationship between Ran expression and the occurrence and progression of cancer, the development of a small molecule compoun...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652411797536688

    authors: Doherty KJ,McKay C,Chan KK,El-Tanani MK

    更新日期:2011-11-01 00:00:00

  • Neuronal Expression of Junctional Adhesion Molecule-C is Essential for Retinal Thickness and Photoreceptor Survival.

    abstract:BACKGROUND:Photoreceptor cell death is a key pathology of retinal degeneration diseases. To date, the molecular mechanisms for this pathological process remain largely unclear. Junctional adhesion molecule-c (Jam-c) has been shown to play important roles in different biological events. However, its effect on retinal ne...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524018666180212144500

    authors: Li Y,Zhang F,Lu W,Li X

    更新日期:2018-03-09 00:00:00

  • SUMOylation Regulation of Retina Development and Functions.

    abstract::The structure and developmental mechanisms of vertebrate retina are highly conserved. One of the most distinctive events during retinogenesis is the temporally and spatially generation of seven types of retinal cells from the multipotent retinal progenitor cells. The importance and prevalence of SUMOylation in regulat...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524016666161128115453

    authors: Zhang L,Li DW

    更新日期:2016-01-01 00:00:00

  • Association of Vitamin D Gene Polymorphisms and Bone Mineral Density in Healthy young Saudi Females.

    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

    authors: Taha IM,Allah AMA,El Tarhouny S

    更新日期:2019-01-01 00:00:00

  • Ipsilateral hippocampal proteomics reveals mitochondrial antioxidative stress impairment in cortical-lesioned chronic mild stressed rats.

    abstract::In this study, a two-dimensional gel-based proteomic approach was applied to profile the protein alterations underlying the significant adverse effects from post-stroke depression (PSD). In view of the close association between left prefrontal cortical dysfunction and PSD, a PSD rat model was constructed through a lef...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524014666141021143333

    authors: Pan J,Liu H,Zhou J,Liu Z,Yang Y,Peng Y,You H,Yang D,Xie P

    更新日期:2014-01-01 00:00:00

  • The many faces of glutathione transferase pi.

    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

    authors: Vasieva O

    更新日期:2011-03-01 00:00:00

  • Interaction of tgf-beta with immune cells in airway disease.

    abstract::Asthma, chronic obstructive pulmonary disorder (COPD), and cystic fibrosis (CF), chronic diseases of the airways, are characterized by symptoms such as inflammation of the lung tissue, mucus hypersecretion, constriction of the airways, and excessive fibrosis of airway tissue. Transforming growth factor (TGF)-beta, a c...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652408785160943

    authors: Moore B,Murphy RF,Agrawal DK

    更新日期:2008-08-01 00:00:00

  • Biomedical applications of zinc oxide nanomaterials.

    abstract::Nanotechnology has witnessed tremendous advancement over the last several decades. Zinc oxide (ZnO), which can exhibit a wide variety of nanostructures, possesses unique semiconducting, optical, and piezoelectric properties hence has been investigated for a wide variety of applications. The most important features of ...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524013666131111130058

    authors: Zhang Y,Nayak TR,Hong H,Cai W

    更新日期:2013-12-01 00:00:00

  • Combating protein misfolding and aggregation by intracellular antibodies.

    abstract::Conformational or misfolding diseases are a large class of devastating human disorders associated with protein misfolding and aggregation. Most conformational diseases are caused by a combination of genetic and environmental factors, suggesting that spontaneous events can destabilize the protein involved in the pathol...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652408783565595

    authors: Cardinale A,Biocca S

    更新日期:2008-02-01 00:00:00

  • The dual role of interleukin-25 in the control of immune-mediated pathologies.

    abstract::Interleukin-25 (IL-25) plays a key role in the initiation and expansion of T helper (Th) 2 cell-mediated immune responses, thereby contributing to allergic diseases and host defense against helminthic parasites. More recent studies have however shown that IL-25 can also control the function of non-T cells, such as ant...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652411794474365

    authors: Caruso R,Stolfi C,De Nitto D,Pallone F,Monteleone G

    更新日期:2011-02-01 00:00:00