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PLoS Negl Trop Dis 16(6):Įditor: Mohamed Gomaa Kamel, Minia University, EGYPT (2022) The polymorphic landscape analysis of GATA1 exons uncovered the genetic variants associated with higher thrombocytopenia in dengue patients. However, this study needs to be replicated in a large number of dengue patients.Ĭitation: Al Rimon R, Sayem M, Alam S, Al Saba A, Sanyal M, Amin MR, et al. We have identified new GATA1 gene variations that were proven to be clinically related to the outcome of dengue patients and hence holds the potential to be candidate biomarkers for determining the severity and prognosis of dengue thrombocytopenia. Patients harboring either nonsynonymous or synonymous variants had significantly lower mean platelet counts compared to those having wild-type nucleotides.

Out of the 13 variations identified, variants G>A (chX:48792009) and C>A (chX:4879118) had the highest frequencies. The exonic polymorphism landscape of hematopoietic transcription factor-GATA1 in dengue patients was investigated in our study to see if there is an association between genetic variations and thrombocytopenia. GATA1 is considered to be the master transcription factor for regulating the differentiation and maturation of megakaryocytes (MKs). Hemorrhagic manifestations in dengue are caused by increased vascular permeability and thrombocytopenia (150K cells/L).

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Trial Registration: number SLCTR/2019/037.ĭengue, a mosquito-borne viral disease, caused by dengue virus (DENV) of the Flaviviridae family has been the source of a global epidemic for decades, and it has recently spread to all parts of the globe. However, further validation of this study in a large number of dengue patients is warranted. 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. 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. 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. Further analyses revealed that the change in amino acid residue leads to the altered three-dimensional structure followed by interaction with neighboring residues. Patients carrying either nonsynonymous or synonymous variants had significantly lower mean values of platelets compared to those harboring the reference nucleotides (NC_000023.11). 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). Polymerase chain reaction using specific primers amplified the exonic regions of GATA1 while Sanger sequencing and chromatogram analyses facilitated the identification of variants. All dengue patients were confirmed through detection of NS1 antigen, IgM, and IgG antibodies against the dengue virus. 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. 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.

Antonym of elucidate