The polymorphic landscape analysis of GATA1 exons uncovered the genetic variants associated with higher thrombocytopenia in dengue patients. | LitMetric
Laboratory of Population Genetics, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh.
Published: June 2022
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Article Abstract
The current study elucidated an association between gene variants and thrombocytopenia through the investigation of the exonic polymorphic landscape of hematopoietic transcription factor-GATA1 gene in dengue patients. A total of 115 unrelated dengue patients with dengue fever (DF) (N = 91) and dengue hemorrhagic fever (DHF) (N = 24) were included in the study. All dengue patients were confirmed through detection of NS1 antigen, IgM, and IgG antibodies against the dengue virus. Polymerase chain reaction using specific primers amplified the exonic regions of GATA1 while Sanger sequencing and chromatogram analyses facilitated the identification of variants. Variants G>A (at chX: 48792009) and C>A (at chX: 4879118) had higher frequency out of 13 variants identified (3 annotated and 10 newly recognized). Patients carrying either nonsynonymous or synonymous variants had significantly lower mean values of platelets compared to those harboring the reference nucleotides (NC_000023.11). Further analyses revealed that the change in amino acid residue leads to the altered three-dimensional structure followed by interaction with neighboring residues. Increased stability of the protein due to substitution of serine by asparagine (S129N at chX: 48792009) may cause increased rigidity followed by reduced structural flexibility which may ultimately disturb the dimerization (an important prerequisite for GATA1 to perform its biological activity) process of the GATA1 protein. This, in turn, may affect the function of GATA1 followed by impaired production of mature platelets which may be reflected by the lower platelet counts in individuals with such variation. In summary, we have identified new variants within the GATA1 gene which were found to be clinically relevant to the outcome of dengue patients and thus, have the potential as candidate biomarkers for the determination of severity and prognosis of thrombocytopenia caused by dengue virus. However, further validation of this study in a large number of dengue patients is warranted. Trial Registration: number SLCTR/2019/037.
The McMaster Immune Thrombocytopenia (ITP) Summit was an educational seminar from leading experts in immune thrombocytopenia and related disorders geared towards hematologists, internists, immunologists, and clinical and translational scientists. The focus of the Summit was to review the mechanisms, diagnosis and treatment of primary versus secondary ITP. Specific objectives were to describe the unique features of secondary ITP, and to review its mechanisms in the context of autoimmune disease and infection.
Dengue infection poses a significant public health challenge in tropical countries. In Thailand, children ages 5-14 years are among the groups with the highest incidence of dengue. This study aimed to determine the prevalence of gastrointestinal (GI) manifestations in children with dengue infection and assess prognostic factors for severe dengue.
Dengue fever, caused by the dengue virus and transmitted by mosquitoes, poses a significant global health threat, particularly in tropical and subtropical regions. Severe cases can manifest as dengue hemorrhagic fever (DHF) or dengue shock syndrome, leading to complications such as plasma leakage, fluid accumulation, respiratory distress, severe bleeding, and organ impairment. Among these complications, gastrointestinal (GI) bleeding is particularly concerning due to its potential to rapidly deteriorate the patient's condition.
Department of Translational Virology, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Katraj-Dhankawadi, Pune 411043, India. Electronic address:
Platelets are essential for hemostasis and vascular integrity. Platelets recognize dengue virus through the DC-SIGN receptor. Upon pathogen recognition, platelets rapidly modulate the expression of adhesion molecules to trigger immune cell interactions and regulate the immune response.
