Examinando por Autor "Roco, A."

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    A Pharmacogenetically Guided Acenocoumarol Dosing Algorithm for Chilean Patients: A Discovery Cohort Study
    (Frontiers Media S.A., 2020-04) Roco, A.; Nieto, E.; Suárez, M.; Rojo, M.; Bertoglia, M.P.; Verón, G.; Tamayo, F.; Arredondo, A.; Cruz, D.; Muñoz, J.; Bravo, G; Salas, P.; Mejías, F.; Godoy, G.; Véliz, P.; Quiñones, L.A.
    Background: Vitamin K antagonists (VKA) are used as prophylaxis for thromboembolic events in patients with cardiovascular diseases. The most common VKA are warfarin and acenocoumarol. These drugs have a narrow therapeutic margin and high inter-individual response variability due to clinical and pharmacogenetic variables. Objective: The authors aim to develop an algorithm comprised of clinical and genetic factors to explain the variability in the therapeutic dose of acenocoumarol among Chilean patients Methodology: DNA was obtained from 304 patients as a discovery cohort with an international normalized ratio (INR) range of 2.0–3.0. The non-genetic (demographic and clinical) variables were also recorded. Genotype analyses were performed using real-time PCR for VKORC1 (rs9923231), VKORC1 (rs7294), GGCx (rs11676382), CYP4F2 (rs2108622), ABCB1 (rs1045642), CYP2C9*2 (rs1799853), ApoE (rs429358), and CYP2C9*3 (rs1057910). Results: The clinical variables that significantly influenced the weekly therapeutic dose of VKA were age, sex, body mass index (BMI), and initial INR, collectively accounting for 19% of the variability, and the genetic variables with a significant impact were VKORC1 (rs9923231), CYP2C9*2 (rs1799853), and CYP2C9*3 (rs1057910), explaining for another 37% of the variability. Conclusion: We developed an algorithm that explains 49.99% of the variability in therapeutic VKA dosage in the Chilean population studied. Factors that significantly affected the dosage included VKORC1, CYP2C9*2, and CYP2C9*3 polymorphisms, as well as age, sex, BMI, and initial INR. © Copyright © 2020 Roco, Nieto, Suárez, Rojo, Bertoglia, Verón, Tamayo, Arredondo, Cruz, Muñoz, Bravo, Salas, Mejías, Godoy, Véliz and Quiñones.
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    Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the chilean population: Comparison with caucasian and asian populations
    (Frontiers Media S.A., 2012-11) Roco, A.; Quiñones, L.; Agúndez, J.; García-Martín, E.; Squicciarini, V.; Miranda, C.; Garay, J.; Farfán, N.; Saavedra, I.; Cáceres, D.; Ibarra, C.; Varela, N.
    Cancer is a leading cause of death worldwide. The cancer incidence rate in Chile is 133.7/100,000 inhabitants and it is the second cause of death, after cardiovascular diseases. Most of the antineoplastic drugs are metabolized to be detoxified, and some of them to be activated. Genetic polymorphisms of drug-metabolizing enzymes can induce deep changes in enzyme activity, leading to individual variability in drug efficacy and/or toxic-ity. The present research describes the presence of genetic polymorphisms in the Chilean population, which might be useful in public health programs for personalized treatment of cancer, and compares these frequencies with those reported for Asian and Caucasian populations, as a contribution to the evaluation of ethnic differences in the response to chemotherapy. We analyzed 23 polymorphisms in a group of 253 unrelated Chilean volunteers from the general population. The results showed that CYP2A6*2, CYP2A6*3, CYP2D6*3, CYP2C19*3, and CYP3A4* 17 variant alleles are virtually absent in Chileans. CYP1A1*2A allele frequency (0.37) is similar to that of Caucasians and higher than that reported for Japanese people. Allele frequencies for CYP3A5* 3(0.76) and CYP2C9* 3(0.04) are similar to those observed in Japanese people. CYP1A1*2C(O.32), CYP1A2* 1F(0.77), CYP3A4* 1B(0.06), CYP2D6*2(0.4V, and MTHFRT(0.52) allele frequencies are higher than the observed either in Caucasian or in Japanese populations. Conversely, CYP2C19* 2 allelic frequency (0.12), and genotype frequencies for GSTT1 null (0.11) and GSTM1 null (0.36) are lower than those observed in both populations. Finally, allele frequencies for CYP2A6* 4(0.04), CYP2C8*3(0.06), CYP2C9* 2(0.06), CYP2D6*4(0.12), CYP2EV5B(0.14), CYP2E1* 6(0.19), and UGT2B7* 2(0.40) are intermediate in relation to those described in Caucasian and in Japanese populations, as expected according to the ethnic origin of the Chilean population. In conclusion, our findings support the idea that ethnic variability must be considered in the pharmacogenomic assessment of cancer pharmacotherapy, especially in mixed populations and for drugs with a narrow safety range. © 2012 Roco, Quiñones, Agúndez, García-Martín, Squicciarini, Miranda, Garay, Farfán, Saavedra, Cáceres, Ibarra and Varela. © 2012 Roco, Quiñones, Agúndez, García-Martín, Squicciarini, Miranda, Garay, Farfán, Saavedra, Cáceres, Ibarra and Varela.
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    Functionally Significant Coumarin-Related Variant Alleles and Time to Therapeutic Range in Chilean Cardiovascular Patients
    (2020) Rojo, M.; Roco, A.; Suarez, M.; Lavanderos, M.; Verón, G.; Bertoglia, M.; Arredondo, A.; Nieto, E.; Rubilar, J.; Tamayo, F.; Cruz, D.; Muñoz, J.
    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.
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    In vitro biocontrol activity of Trichoderma harzianum on Alternaria alternata in the presence of growth regulators
    (Electronic Journal of Biotechnology, 2001-08) Roco, A.; Pérez, L.
    The in vitro biocontrol ability of Trichoderma harzianum on the phytopathogen Alternaria alternata improved in the presence of the growth regulators gibberellic acid (GA3), or indolacetic acid (IAA) or benzylaminopurine (BAP) or foliar nutrient at concentrations similar or higher than those used at the field level. These plant hormones decreased the secretion of endopolygalacturonase (endo-PG) of A. alternata by approximately 20%, did not modify endochitinase (endo-CH) secretion of T. harzianum and did not alter germination of conidia or mycelia growth of any of these fungi. The presence of T. harzianum decreased endo-PGase secretion of A. alternata by about 50%. This inhibitory effect was independent of the presence of growth regulators. The level of secreted endo-PG of T. harzianum was not modified by the presence of A. alternata, but the presence of this phytopathogen in cultures of T. harzianum, increased both the growth of the biocontroller and its secretion of endo-CH.