Search

Regulatory agencies such as the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) recognize pharmacogenetics as a key tool in their pharmacological guidelines for pharmaceutical counseling. In this context, community pharmacies play a crucial role in addressing this healthcare need, which could lead to a significant improvement in patients' quality of life by preventing ineffective or contraindicated treatments. In this work, we conducted a systematic review of the available scientific evidence regarding druggene interactions relevant to community pharmacy. We identified the main genes and polymorphisms associated with treatment response and adverse effects in primary care. Finally, we propose a model for implementing pharmacogenetic services in community pharmacies. [ABSTRACT FROM AUTHOR]

Introduction: Warfarin is an anticoagulant whose efficacy depends on reaching and maintaining an INR (International Normalized Ratio) within therapeutic ranges. Up to 60% of interindividual dose-response variability can be explained by pharmacogenes, in this regard there are no studies in Peru. We studied the effect of the CYP4F2 gene on the dose of warfarin in Peruvian patients. Material and Methods: A descriptive and ambispective observational study was carried out with patients seen in the Grau ESSALUD Hospital Hematology Service, Lima, Peru, selected by non-probabilistic convenience sampling. The inclusion criteria were patients anticoagulated for more than three months and with stable doses of warfarin (same dose for at least three outpatient visits and with an INR in therapeutic ranges of 2.5-3.5). Analysis of the CYP4F2 gene was performed by taking a DNA sample from peripheral blood. Results: 70 patients with a mean age of 69.6 + 13.4, male 38 (54.39%) and female 32 (45.7%) entered the study. The mean dose of warfarin was 31.6 + 15.2 mg/week. The genotypic frequency of the CYP4F2 gene, rs2108622 variant (C>T) was 55 (78%), 13 (19%) and 2 (3%) of CC, CT, TT, respectively. No deviation from the Hardy-Weinberg equilibrium was found in the variants studied (p=0.56). Mean warfarin doses/week of the CC, CT, TT genotypes were 30.34 + 11.98; 36.4 + 25.6 and 36.25 + 1.8 mg/week, respectively (p=0.397). Conclusion: In conclusion, it appears that CYP4F2 gene genotypes do not have a significant effect on warfarin dose. [ABSTRACT FROM AUTHOR]

Copyright of Advances in Laboratory Medicine / Avances en Medicina de Laboratorio is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Variations in drug metabolism are based on constitutional, genetic and environmental factors; therefore, knowing the type and allelic frequencies of the CYP2D6 gene polymorphism in patients with Huntington's disease is relevant in the application and efficacy of available pharmacological treatments that are beneficial and improve their quality of life. Aim: To establish the allelic and genotype frequencies of the CYP2D6 gene: *3, *4, *5 and *6 in a population sample of patients with Huntington's disease in Juan de Acosta, Colombia. Material and methods: Cross-sectional study, with non-probabilistic convenience sampling consisting of 23 individuals: 10 patients with signs and symptoms of the condition, 5 relatives and 8 unrelated people. After signing the informed consent, DNA was isolated and quantified in peripheral blood samples using a UV-Vis spectrophotometer. The identification of polymorphism: *3, *4 and *6 was performed by Variant RFLP-conventional PCR and digestion with endonucleases. The *5 allele and CYP2D6 gene duplication were genotyped by multiplex real PCR. Results: In the population sample, the CYP2D6 *4 and *6 alleles have frequencies 0.304 and 0.435, respectively; CYP2D6 *3 is monomorphic; assuming population genetic equilibrium, the frequency of the mutated allele *5 is 0.295 and 0.511, the CYP2D6 duplication. Conclusions: The most represented genotype in the population was the wild type *1/*1 of CYP2D*3, homozygous, the genotype *4/*4 with mutated allele represents 30.4%; finally, a frequency of 26.1% with duplication/multiplication of active CYP2D6 alleles, a higher value than those reported in the Hispano-American and Colombian populations. [ABSTRACT FROM AUTHOR]

The article discusses acute liver transplant rejection and its relationship with CYP3A5 and MDR-1 enzyme polymorphisms. It is mentioned that acute rejection in this type of transplant is multifactorial and that polymorphisms in more than one gene are essential in determining the transplant prognosis. The direct association between interleukin-17 G-197A polymorphisms and acute liver transplant rejection is highlighted. Additionally, it is mentioned that microRNAs also have effects on tacrolimus metabolism, which can influence acute transplant rejection. [Extracted from the article]

Copyright of Acta Médica Peruana is the property of Colegio Medico del Peru and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Médica Clínica Las Condes is the property of Editorial Sanchez y Barcelo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Médica Clínica Las Condes is the property of Editorial Sanchez y Barcelo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Pharmacogenomics is the science that studies the role of the different components of the human genome on response to drugs. Knowing the information on these factors could be useful in the field of psychopharmacology of children and adolescents in order to individualize the selection of treatments and minimize adverse reactions. Material and methods: A literature review of the publications of the last ten years was carried out in the PubMed database, using the following keywords: Psychiatry AND child and adolescent AND pharmacogenomics; Psychiatry AND child and adolescent AND pharmacogenomic/pharmacogenetic. 35 articles were selected following previously established inclusion criteria. Results: The most consistent results are those related to the polymorphisms of the CYP450 family genes, especially the different metabolising phenotypes (slow, intermediate, fast) that influence pharmacological response to Selective Serotonin Reuptake Inhibitors (SSRIs), Risperidone and Atomoxetine. Furthermore, functional polymorphisms of the HTR2A gene are related to the clinical response to SSRIs and several COMT polymorphisms are related to a decreased response to Methylphenidate and other stimulants. Serotonergic receptor variants such as 5HT2A, 5HT1B also influence the response and likelihood of SSRIs' side effects. Conclusions: The use of pharmacogenetic tests may become a complementary tool in therapeutic decision-making in Child and Adolescent Psychiatry. However, in light of the results reviewed, its widespread use is not justified, although it could be considered in some patients with severe diseases and insufficient response to previously tested drugs. [ABSTRACT FROM AUTHOR]

We present the clinical case of a 10-year-old patient diagnosed with dilated cardiomyopathy who registered INR values above 10 upon receiving standard doses of acenocoumarol, as well as other values reported as uncoagulable, forcing the discontinuation and restart of treatment more than once. Expected and stable INR levels were achieved after more than 30 days of treatment, surprisingly with half the recommended dose for a patient of her age and weight. We decided to conduct a retrospective pharmacogenomic analysis including nucleotide genetic polymorphisms (SNPs) with different degrees of association with the dose/response to antivitamin K (AVK) drugs: rs2108622 (gene CYP4F2), rs9923231, rs7294 (gene VKORC1), rs1799853, and rs1057910 (CYP2C9 gene) using TaqMan® RT-PCR. The patient was homozygous for rs9923231 (VKORC1) and heterozygous for rs2108622 (CYP4F2), a genetic profile strongly associated with a requirement of lower AVK doses as shown by national and international evidence. In conclusion, the pharmacogenetic analysis confirmed that this patient's genetic conditions, involving low expression of the VKA therapeutic target, required a lower dose than that established in clinical protocols as recommended by the Food and Drug Administration (FDA) and the PharmGKB® for coumarin drugs. A previous genotypic analysis of the patient would have allowed reaching the therapeutic range sooner, thus avoiding potential bleeding risks. This shows the importance of pharmacogenetic analyses for highly variable treatments with a narrow therapeutic range. [ABSTRACT FROM AUTHOR]

Copyright of Biomédica: Revista del Instituto Nacional de Salud is the property of Instituto Nacional de Salud of Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Habanera de Ciencias Médicas is the property of Universidad de Ciencias Medicas de La Habana and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Biomédica: Revista del Instituto Nacional de Salud is the property of Instituto Nacional de Salud of Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Médica Clínica Las Condes is the property of Editorial Sanchez y Barcelo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Biomédica: Revista del Instituto Nacional de Salud is the property of Instituto Nacional de Salud of Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To determine the frequency of the C282T polymorphism of the NAT2 gene (N acetyltransferase) in Peruvian populations. Field work, focused on exploring genetic risk factor in Peruvian populations, which has influence in the response to drugs and malignancies aetiology. Material and Methods: Cross-sectional study. 166 voluntaries from Lima, Lambayeque, Apurimac, Puno, San Martin, Amazonas and Loreto were enrolled. The sampling was done by convenience and it was use the RFLP-PCR conventional technique was used. Results: The allele frequency were 54% (n=126) for C282 and 46% (n=106) for T282. For the T allele, by its orign, stand out 2 those which origins were Lima 42% (n=25), Amazonas 47% (n=16), San Martin 74% (n=28) and Apurimac 50% (n=13) (X, p>0.05). A global genotype frequency were 26.7% (n=31) for C282/C282, 56.0% (n=65) for C282/T282 and 17.2% (n=20) for T282/T282 (Hardy Weinberg Test p>0.05). By origin, Puno presented allelic imbalance (Hardy Weinberg test p<0.05) and the others populations presented allelic balance (Hardy Weinberg test p>0.05). Conclusion: The overall frequency of NAT2 allele T282 was 46%; San Martin had the highest prevalence (74%). The T282 allele is linked to neoplastic diseases and adverse reactions to anti-TB drugs, these results will be used for the application of pharmacogenetics in Peru. [ABSTRACT FROM AUTHOR]

In recent years, with the rise of technology and specialization, the concept of person-centered medicine has been introduced. It emphasizes on individual care of patients as subjects using a holistic, general and non-fragmented approach, which considers the human being in all its biopsychosocial dimensions. At the same time, another term has been introduced: the personalized medicine or precision medicine, which primarily aims to optimize the prescription of specific therapies tailored to the individual characteristics of each person, based on available pharmacogenetic and pharmacogenomic information. Although, it is also stated that preventive and diagnostic actions may arise from it. These two approaches are not antagonistic; on the contrary, they can complement each other for the patient's benefit. The assertion that "there are no diseases, but sick people" becomes topical again. [ABSTRACT FROM AUTHOR]

Tuberculosis is a health problem worldwide with one-third of the population infected with the Mycobacterium tuberculosis bacilli. The first-line of treatment for tuberculosis includes the drugs Isoniazid (INH) and Rifampicin (RIF) metabolized in the liver. Drug metabolism is directly related to the genetic variation of NAT2 and CYP2E1 (associated with INH metabolism) and AADAC (associated with RIF metabolism), and the effects produced in an individual may be a fast, intermediate or slow metobolizer. Polymorphisms in genes of people in standard tuberculosis treatment can cause effects on drug metabolism with consequences of hepatotoxicity and even drug resistance. Countries have began clinical trials focusedon personalization of tuberculosis treatment to reduce the consequences for patients in treatment. In countries like Peru, where high rates of tuberculosis are recorded and therefore more people in treatment, the pharmacogenomic of individuals becomes a crucial tool for an optimum tuberculosis treatment. This review highlights the importance of having pharmacogenomic studies and having the identification of polymorphisms associated to the metabolism of the anti-tuberculosis drugs in our Peruvian population. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the CYP2D6: * 4, * 6 and * 10 gene variants frequency and to predict the metabolizer phenotype in a sample of 145 unrelated apparently healthy individuals residing in the state of Aragua, Venezuela. Genotypes were determined by Polymerase chain reaction assays followed by restriction endonucleases digestion. The metabolizer phenotype prediction was made based on the activity score system. The frequencies of CYP2D6 * 4, * 6 and * 10 allelic variants were 14.5%, 0.3% and 1%. A significant percentage of individuals were categorized as heterozygote-extensive/intermediate (23.5%) and poor metabolizers (4.1%), this information has potential clinical impact, because the CYP2D6 protein is involved in the metabolism of drugs frequently prescribed as: carvedilol, captopril, chloroquine, codeine, fluoxetine, fluvastatin, haloperidol, idarubicin, indinavir, imatinib, loperamide, nifedipine, ondansetron and tamoxifen. [ABSTRACT FROM AUTHOR]

Introduction: Leukotrienes are molecules from different cells, derived from arachidonic acid by the 5-lipoxygenase pathway; they are involved in some processes that damage organs and tissues. This led researchers to develop antagonists to stop the consequences they bring to the body. Methodological design: We conducted a bibliographic review that amounted to a total of 27 articles consulted. Objective: In order to argue the significance of leukotrienes and anti-leukotrienes in evidence-based medicine. Conclusions: We found that bronchial asthma and allergic rhinitis are examples of pathologies in which anti-leukotrienes can be useful; we stress the importance of pharmacogenetics in the association of the polymorphism with their evident clinical response. [ABSTRACT FROM AUTHOR]

We conducted a review of the results of the studies of the last ten years from the data bases BBCS-LILACS, IB- PsycINFO, IB-SSCI, IB.SciELO, SCOPUS and SCIRUS, about the therapeutic implications of the gene mutation ABCB1 in dogs. This mutation is responsible for the absence of the glycoprotein P in the bloodbrain barrier, depriving the brain of an efflux pump to protect against various xenobiotics. Furthermore, we described the pharmacokinetic changes and drug poisoning resulting from this mutation. We also present a list of drug substrates for the glycoprotein P and the medications that can inhibit said glycoprotein, all of them capable of inducing severe side effects in dogs with the mutation. [ABSTRACT FROM AUTHOR]

Copyright of Investigaciones ANDINA is the property of Fundacion Universitaria del Area Andina and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Médica Clínica Las Condes is the property of Editorial Sanchez y Barcelo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Médica Clínica Las Condes is the property of Editorial Sanchez y Barcelo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Médica Clínica Las Condes is the property of Editorial Sanchez y Barcelo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An individual's ability to metabolize certain drugs depends on multiple factors, including its genetic profile. Patients with altered expression of certain enzymes can have an decreased or increased clearance of the administered drug, causing therapeutic failure, risk of intoxication or adverse effects. It has been reported that most pharmaceutical drugs are effective in a range from 25% to 60%. The aim of this article is to define fundamental aspects of pharmacogenetics and pharmacogenomics, addressing particular cases such as the metabolism of the thiopurine-methyl-transferase-enzyme and the CYP2C19 hepatic microsomal system and present results about the metabolism of proton pump inhibitors, generated by our group. It is stated that pharmacogenetics and pharmacogenomics are new fields of study, which are constantly evolving. We consider noteworthy for the doctor to know a patient's genotype because there is a variation in the metabolism of certain drugs depending on the studied population. Therefore, a global treatment for a given disease can not be generalized. This highlights the importance of a tailored-based pharmacological therapy in order to prescribe the treatment at optimal doses, improving the patient's quality of life and clinical outcome. [ABSTRACT FROM AUTHOR]

Based on present knowledge, in this work we review the importance of the pharmacogenetic tests in the treatment with antipsychotic drugs. Many associations have been reported between different genetic markers and response to treatment as well as to the appearance of adverse reactions. However, up to now, no "prime" biomarker capable of unequivocally predicting the clinical benefits of a specific treatment or its toxicity has been identified. The use of individual pharmacogenetic markers has been demonstrated to have little clinical utility, and therefore the combination of information obtained from the analysis of different genes seems to be a more promising strategy. Inclusion of pharmacogenetic tests in clinical trials conducted prospectively and that include a large number of cases could, undoubtedly, significantly contribute to the development of individualized medicine protocols. [ABSTRACT FROM AUTHOR]

Copyright of Biomédica: Revista del Instituto Nacional de Salud is the property of Instituto Nacional de Salud of Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Medicina (Buenos Aires) is the property of Medicina (Buenos Aires) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Investigaciones ANDINA is the property of Fundacion Universitaria del Area Andina and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Alter the whole genome sequentiation, there is a bigger gap between the capabilities of biomedical technology and the diagnostic of the clinician on its practice. One of the genomic sciences is the pharmacogenomics; the discipline, like its predecessor, pharmacogenetics, attemps to predict the way a specific individual reacts to a medicament, formerly called "medicament idiosyncrasy", with the aim of personalize the therapy. The objective of this article is to make a simple review of the genetic basis of medicament response with a clinical importance. [ABSTRACT FROM AUTHOR]

Introduction: Pharmacogenomics studies how changes in the genome influence the response to drugs. Its main medical value consists in: i) the identification of individuals in which it is possible to predict if certain drug and dose will be effective or on the contrary, if the drug must be avoided due to its high toxicity risk or because the patient will never respond to it; ii) to identify molecular targets able to be intervened by drugs. Objective: To carry out a systematic review about pharmacogenomic oriented to the use and clinical impact of drugs. Methodology: The pertinent biomedical literature was searched in several databases such as Medline, Proquest, Science Direct, Ovid and Cochrane, as well as the available information in web sites of international sanitary organizations. [ABSTRACT FROM AUTHOR]

Introduction: Imatinib is an inhibitor of the BCR-ABL tyrosine-kinase that has dramatically changed the treatment of patient with Chronic myeloid leukemia (CML) positive for the Philadelphia chromosome (Ph+). This compound is mainly metabolized by the cytochrome CYP3A4 enzyme, coded by a gene with individual variations that could interfere with the effectiveness of the treatment, due to the fact that particular single nucleotide polymorphisms (SNPs), i.e., CYP3A4*1B y CYP3A4*2, have shown to exert a significant influence on the metabolic activity of this pharmacologically important enzyme. Objective: Evaluate the frequency of pharmacogenetically important polymorphisms in the CYP3A4 gen in a Colombian population of patients with CML being treated with this novel drug (Imatinib), in parallel with a control population of 164 healthy individuals. Correlate the evolution of the clonal expansion Ph(+) with the presence of these SNPs and the length of treatment. Methodology: PCR-RFLP genotyping for the CYP3A4* 1B y CYP3A4*2 SNPs. RBHG replication banding for the evaluation of the presence of the Ph(+) markers in spontaneous mitotic blasts. Results: A positive cytogenetic response and/or correlation was detected between the length of the imatinib treatment and a reduction in the percentage of Ph(+) blasts. Genotyping indicate that CYP3A4*1B polymorphism does no affect the cytogenetic response in imatinib treated Ph(+) patients, and that the pharmacorelevant CYP3A4*2 SNP is not present in this population of patients and controls (N=194). Conclusions: The pharmacogenotype CYP3A4*2 (exon 7) does not affect the induced positive cytogenetic response triggered by the imatinib treatment, that generally induces a reduction in Ph(+) blasts en relation with the duration of the treatment. [ABSTRACT FROM AUTHOR]

Pharmacogenomics studies the influence of hereditary factors in determining individual differences in response to drugs. Its main objective is the study of genes and their activity, toxicity and metabolism in drug reactions, as well as the righteous way to prescribe any treatment and its specific dosage with less toxicity for each patient. One of the goals of the pharmacogenomics is to determine whether the expression of the gene influences the efficacy of a drug by affecting its metabolism, availability at the site of action (pharmacokinetics), and by the way the drug binds to its target receptors and achieves a desired pharmacologic action (pharmacodynamics). There are three main enzyme systems in the human body in charge of drug metabolism: the Cytochrome P-450, N-acetyltransferases types 1 and 2, and thiopurine methyltransferase. Nevertheless, many non-genetic factors influence the effects of medications, including age, organ function, concomitant therapy, drug interactions, alcohol intake, smoking, infections, and the nature of the disease. [ABSTRACT FROM AUTHOR]

Cutaneous drug reactions (cADRs) are the most frequent adverse drug reactions with important consequences in morbidity, mortality and hospital costs. In recent years, pharmacogenetics has allowed recognition of important markers of genetic susceptibility to the development of adverse drug reactions; in dermatology, it has shown significant associations between cADRs and genes involved in metabolic pathways and drug detoxification as well as with the major histocompatibility complex, regulator of immune responses. Pharmacogenetics has also led to the support, and refusal, of basic notions in the physiopathogenics of cADRs. Knowledge regarding the differences among pharmacogenetics and pharmacoethnias may alert physicians for adequate therapeutic options, their dosage, or the need for rigorous monitoring; it is feasible in the near future to envisage having a personal registry of the genetic profile that could be consulted previous to drug prescription. [ABSTRACT FROM AUTHOR]

El proyecto ChocoGen se creó para facilitar los estudios genómicos de la población predominantemente afrodescendiente del Chocó, en la costa del pacífico colombiano. ChocoGen tiene como objetivos: (1) caracterizar la ancestría genética de la población del Chocó, y (2) explorar la relación entre la ancestría y los determinantes genéticos de la salud en la región. La ancestría genética del Chocó es predominantemente africana (76%) con fracciones equitativas europeas (13%) y nativas americanas (11%), mientras que la población vecina de Antioquia tiene una ancestría principalmente europea (75%), seguida de nativa americana (18%) y africana (7%). Exploramos la relación entre la ancestría genética y la respuesta a medicamentos para estas dos poblaciones. Encontramos un número de variantes farmacogenéticas que muestran grandes diferencias en sus frecuencias alélicas y estas diferencias están asociadas con ancestrías distintas. Por ejemplo, una variante que se asocia con un mayor riesgo de toxicidad para una estatina prescrita comúnmente, se encuentra con una frecuencia relativamente alta en Antioquia y se asocia con la ancestría europea. Nuestros colaboradores en GenomaCES han desarrollado un ensayo de PCR alelo-específica de bajo costo para detectar la presencia de estos SNP farmacogenéticos enriquecidos poblacionalmente en entornos de recursos limitados como el de Colombia. [ABSTRACT FROM AUTHOR]

El Consorcio Internacional de Farmacogenetica de la Warfarina (IWPC) realizó un estudio en 4 continentes buscando determinar el algoritmo predictivo de la dosis terapéutica. Adicionalmente, en Colombia se publicaron tres algoritmos (Palacio, Isaza y Cifuentes). En consecuencia, se compara su valor predictivo para sugerir un algoritmo para predecir la dosis terapéutica de Warfarina en población mestiza colombiana. Mediante regresión lineal simple, se compararon las dosis reales en la población estudiada por Cifuentes, con predicha por los algoritmos IWPC, Isaza y Palacio. Para entender los resultados, se compararon los algoritmos predictivos con el más explicativo obtenido mediante regresión lineal múltiple por Cifuentes en el Hospital Militar Central. IWPC mostró mayor exactitud de predicción, seguido de Palacio e Isaza (R2= 0,45, 0,35 y 0,29 respectivamente). Todos los algoritmos predictores incluyeron las variantes 1639G>A en VKORC1 y *2/*3 en CYP2C9 además de Edad en concordancia con el algoritmo explicativo. El único algoritmo con variables asociadas al Sexo fue IWPC: Talla y Peso (p<0,001). Se sugiere la utilidad del algoritmo IWPC, favoreciendo el alto poder estadístico para determinar coeficientes y variables relevantes. [ABSTRACT FROM AUTHOR]

El cáncer de seno está conformado por un grupo de enfermedades multigénicas con gran impacto a nivel mundial. Para su tratamiento, existen diversas alternativas terapéuticas, una de ellas, la hormonoterapia; donde tamoxifeno (TAM) es el medicamento de primera elección. El tamoxifeno requiere la acción de la enzima CYP2D6 para su biotransformación y es conocido que la variabilidad genética de esta, condiciona la presencia de diversos fenotipos que inciden en la capacidad de metabolizar tamoxifeno. Para establecer las frecuencias alélicas de variantes en CYP450 se procesaron muestras de 30 pacientes con cáncer ductal infiltrante. Las variantes funcionales con actividad normal identificadas en las pacientes fueron: CYP2D6*1, CYP2D6*2A y CYP2D6*35, para el caso de las variantes no funcionales se identificaron CYP2D6*3 y CYP2D6*4. Finalmente, para las variantes con actividad reducida en la población se identificaron CYP2D6*9, CYP2D6*17 y CYP2D6*41. Para las dos pacientes pobres metabolizadoras se realizó modelamiento molecular, donde se mostró que las variantes en CYP2D6 no están en el sitio de unión con tamoxifeno pero si están afectando la plasticidad de la proteína, generando mayor rigidez en la estructura y bloqueo en uno de los túneles de ingreso, situación que estaría incidiendo en la interacción de tamoxifeno y CYP2D6. [ABSTRACT FROM AUTHOR]