Trial reportScientific reports2026
Genetic variability in thrombopoietin receptor and GATA1 influences response to eltrombopag in dengue-induced thrombocytopenia.
Trial report in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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11 authors.
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Abstract
Integrating pharmacogenetic studies into clinical trials enhances personalized medicine by identifying genetic variations that influence drug efficacy and safety. Eltrombopag, a thrombopoietin receptor agonist, has shown efficacy in treating thrombocytopenia associated with various conditions, including dengue fever, though variability in patient response remains poorly understood. This study investigates the impact of genetic variants in the thrombopoietin receptor (TPOR) and GATA1 transcription factor on eltrombopag response in dengue-induced thrombocytopenia. Exonic and flanking region variants of TPOR and GATA1 were analyzed by Sanger sequencing in patients enrolled in a phase-II trial of eltrombopag. Univariate and multivariate logistic regression analyses were performed to assess associations between genetic variants and drug response. The TPOR variant Ch1:43804387T > G (S129R) was linked to slower natural recovery in the control group, with significantly lower platelet counts from day 3 onwards (p < 0.05) in heterozygous carriers, while eltrombopag treatment restored recovery to wild-type levels. Additionally, double mutants of Ch1:43804387T > G and Ch1:43804421 C > A (intronic) showed a compounded disadvantage in natural recovery, which was mitigated by eltrombopag. Patients heterozygous for Ch1:43803796G > A (E36K) exhibited significantly reduced treatment efficacy, with lower platelet counts from day 2 onwards (p < 0.05). In contrast to TPOR variants, the GATA1 variants ChX:48792009G > A (S129N) was associated with significantly faster natural platelet recovery in the control group (p < 0.05). However, logistic regression analysis did not identify any specific variant as a statistically significant independent predictor of binary treatment response (Responder vs. Non-responder at Day 7). The study suggests TPOR variants as potential biomarkers for predicting eltrombopag response, while GATA1 variants may influence natural recovery dynamics in dengue-induced thrombocytopenia. These findings contribute to patient stratification and optimized therapeutic strategies. Further research combining pharmacogenetic and pharmacokinetic factors is essential for fully understanding eltrombopag response variability and advancing personalized treatment approaches.
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