Functionally Significant Coumarin-Related Variant Alleles and Time to Therapeutic Range in Chilean Cardiovascular Patients

Indexación: Scopus.Despite the development of new oral agents over the last decade, vitamin K antagonists (VKAs) remain the most widely used anticoagulants for treating and preventing thromboembolism worldwide. In Chile, the Ministry of Health indicates that acenocoumarol should be used in preference to any other coumarin. Complications of inappropriate dosing are among the most frequently reported adverse events associated with this medication. It is well known that polymorphisms in pharmacokinetic and pharmacodynamic proteins related to coumarins (especially warfarin) influence response to these drugs. This work analyzed the impact of CYP2C19*2 (rs4244285), CYP1A2*1F (rs762551), GGCx (rs11676382), CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), CYP4F2 (rs2108622), VKORC1 (rs9923231), VKORC1 (rs7294), CYP3A4*1B (rs2740574), and ABCB1 (rs1045642) polymorphisms on time to therapeutic range for oral anticoagulants in 304 Chilean patients. CYP2C9*3 polymorphisms were associated with time to therapeutic range for acenocoumarol in Chilean patients, and the CYP4F2 TT genotype, MDR1 A allele, CYP1A2 A allele, and CYP3A4T allele are promising variants that merit further analysis. The presence of polymorphisms explained only 4.1% of time to therapeutic range for acenocoumarol in a multivariate linear model. These results improve our understanding of the basis of ethnic variations in drug metabolism and response to oral anticoagulant therapy. We hope that these findings will contribute to developing an algorithm for VKA dose adjustment in the Chilean population in the near future, decreasing the frequency of stroke, systemic embolism, and bleeding-related adverse events.https://journals.sagepub.com/doi/10.1177/107602962090915

Un examen actualizado de la percepción de las barreras para la implementación de la farmacogenómica y la utilidad de los pares fármaco/gen en América Latina y el Caribe

La farmacogenómica (PGx) se considera un campo emergente en los países en desarrollo. La investigación sobre PGx en la región de América Latina y el Caribe (ALC) sigue siendo escasa, con información limitada en algunas poblaciones. Por lo tanto, las extrapolaciones son complicadas, especialmente en poblaciones mixtas. En este trabajo, revisamos y analizamos el conocimiento farmacogenómico entre la comunidad científica y clínica de ALC y examinamos las barreras para la aplicación clínica. Realizamos una búsqueda de publicaciones y ensayos clínicos en este campo en todo el mundo y evaluamos la contribución de ALC. A continuación, realizamos una encuesta regional estructurada que evaluó una lista de 14 barreras potenciales para la aplicación clínica de biomarcadores en función de su importancia. Además, se analizó una lista emparejada de 54 genes/fármacos para determinar una asociación entre los biomarcadores y la respuesta a la medicina genómica. Esta encuesta se comparó con una encuesta anterior realizada en 2014 para evaluar el progreso en la región. Los resultados de la búsqueda indicaron que los países de América Latina y el Caribe han contribuido con el 3,44% del total de publicaciones y el 2,45% de los ensayos clínicos relacionados con PGx en todo el mundo hasta el momento. Un total de 106 profesionales de 17 países respondieron a la encuesta. Se identificaron seis grandes grupos de obstáculos. A pesar de los continuos esfuerzos de la región en la última década, la principal barrera para la implementación de PGx en ALC sigue siendo la misma, la "necesidad de directrices, procesos y protocolos para la aplicación clínica de la farmacogenética/farmacogenómica". Las cuestiones de coste-eficacia se consideran factores críticos en la región. Los puntos relacionados con la reticencia de los clínicos son actualmente menos relevantes. Según los resultados de la encuesta, los pares gen/fármaco mejor clasificados (96%-99%) y percibidos como importantes fueron CYP2D6/tamoxifeno, CYP3A5/tacrolimus, CYP2D6/opioides, DPYD/fluoropirimidinas, TMPT/tiopurinas, CYP2D6/antidepresivos tricíclicos, CYP2C19/antidepresivos tricíclicos, NUDT15/tiopurinas, CYP2B6/efavirenz y CYP2C19/clopidogrel. En conclusión, aunque la contribución global de los países de ALC sigue siendo baja en el campo del PGx, se ha observado una mejora relevante en la región. La percepción de la utilidad de las pruebas PGx en la comunidad biomédica ha cambiado drásticamente, aumentando la concienciación entre los médicos, lo que sugiere un futuro prometedor en las aplicaciones clínicas de PGx en ALC.Pharmacogenomics (PGx) is considered an emergent field in developing countries. Research on PGx in the Latin American and the Caribbean (LAC) region remains scarce, with limited information in some populations. Thus, extrapolations are complicated, especially in mixed populations. In this paper, we reviewed and analyzed pharmacogenomic knowledge among the LAC scientific and clinical community and examined barriers to clinical application. We performed a search for publications and clinical trials in the field worldwide and evaluated the contribution of LAC. Next, we conducted a regional structured survey that evaluated a list of 14 potential barriers to the clinical implementation of biomarkers based on their importance. In addition, a paired list of 54 genes/drugs was analyzed to determine an association between biomarkers and response to genomic medicine. This survey was compared to a previous survey performed in 2014 to assess progress in the region. The search results indicated that Latin American and Caribbean countries have contributed 3.44% of the total publications and 2.45% of the PGx-related clinical trials worldwide thus far. A total of 106 professionals from 17 countries answered the survey. Six major groups of barriers were identified. Despite the region’s continuous efforts in the last decade, the primary barrier to PGx implementation in LAC remains the same, the “need for guidelines, processes, and protocols for the clinical application of pharmacogenetics/pharmacogenomics”. Cost-effectiveness issues are considered critical factors in the region. Items related to the reluctance of clinicians are currently less relevant. Based on the survey results, the highest ranked (96%–99%) gene/drug pairs perceived as important were CYP2D6/tamoxifen, CYP3A5/tacrolimus, CYP2D6/opioids, DPYD/fluoropyrimidines, TMPT/thiopurines, CYP2D6/tricyclic antidepressants, CYP2C19/tricyclic antidepressants, NUDT15/thiopurines, CYP2B6/efavirenz, and CYP2C19/clopidogrel. In conclusion, although the global contribution of LAC countries remains low in the PGx field, a relevant improvement has been observed in the region. The perception of the usefulness of PGx tests in biomedical community has drastically changed, raising awareness among physicians, which suggests a promising future in the clinical applications of PGx in LAC

Smartphone screen testing, a novel pre-diagnostic method to identify SARS-CoV-2 infectious individuals

The COVID-19 pandemic will likely take years to control globally, and constant epidemic surveillance will be required to limit the spread of SARS-CoV-2, especially considering the emergence of new variants that could hamper the effect of vaccination efforts. We developed a simple and robust - Phone Screen Testing (PoST) - method to detect SARS-CoV-2-positive individuals by RT-PCR testing of smartphone screen swab samples. We show that 81.3-100% of individuals with high-viral-load SARS-CoV-2 nasopharyngeal-positive samples also test positive for PoST, suggesting this method is effective in identifying COVID-19 contagious individuals. Furthermore, we successfully identified polymorphisms associated with SARS-CoV-2 Alpha, Beta, and Gamma variants, in SARS-CoV-2-positive PoST samples. Overall, we report that PoST is a new non-invasive, cost-effective, and easy-to-implement smartphone-based smart alternative for SARS-CoV-2 testing, which could help to contain COVID-19 outbreaks and identification of variants of concern in the years to come