Future directions: challenges, opportunities and limitations

The ultimate goal of pharmacogenomic research is to predict individual's responses to drug therapy and subsequently adapt pharmacotherapeutic strategies. Therefore, the current challenge for personalized therapy is to define genetic profiles to predict the response to drugs and the progression of the diseases. However, despite the enormous amount of known information about the genetic basis of variable response to drugs, it has little influence on its application to the current clinical practice, particularly in Latin American region where there is a great genetic admixture. Thus, the present chapter pursues to contribute with a general vision of the future of the area to overcome the proper limitations of this region

The incorporation of clinical guidelines of pharmacogenomics in Latin America

In Latin America the Pharmacogenetics and Pharmacogenomics areas are recently emerging fields and the main focus of the research is to evaluate ethnic differences to apply adapted guidelines to manage personalized pharmacotherapy. Large differences between countries in the awareness and in the use of pharmacogenomic testing are presumed, but are not well assessed to date. In this chapter, we present the efforts to investigate variability in drug response using the molecular approaches and the limitations to apply pharmacogenomics test in clinical centers and hospitals

Interchangeability of biological drugs: Considerations about the approval of biogeneric formulations in Chile

Once drug patents expire, the health authorities can approve the registry of similar products. They must request to the manufacturer the bibliographic background of the original product and the analytical results that certify drug quality. An inspection of the premises of the manufacturer is also required. The main goal of Ibis approval is to decrease cost, considering that the original product is usually more expensive. This is a current situation due to the imminent expiration of the patents of many biopharmaceutical products. Therefore, in Chile, the Public Health (ISP) and the Ministry of Health should consider that for this kind of products, until now, there are no interchangeable generic drugs, and that the similar drugs that are offered have a different chemical composition, since they have been manufactured through different processes, In the case of biological drugs (e.g. erythropoietir, somatotropin, heparin) the quality and homogeneity depend from the manufacture process. Its complete composition can not be absolutely elucidated; therefore small impurities or conformational variants can elicit an altered immune response or unexpected adverse reactions. This indicates that the approval of a biogeneric drug requires in addition to pharmacokinetic studies, preclinical and clinical analytical studies such as physicochemical assays, biological and immunological test. This issues have been established by WHO and have been incorporated for the main drug registry entities all over the world (FDA, EME4, ANVISA) to approve biogeneric products

Pharmacogenomics in psychiatric practice: Latin America initiatives

Pharmacogenomics has had a good development in most of medical specialties, nevertheless in psychiatry has been particularly successful. Accordingly, it has been extremely useful in psychiatric patients considering how common is the use of therapeutic regimens that combine several drugs with significant interactions between them. Patients with complex pathologies such as bipolar affective disorder, major depression, psychotic depression, borderline personality disorder, organic brain damage with uncontrolled impulses, among others, have medical advice that is necessary to obtain their genotype profile. In some of these patients, the genotyping results may involve to withdraw some drugs, decrease doses, avoid certain combinations of drugs, or continue using high doses or complex combination therapies with greater confidence. In this respect, CYP2D6 is a biotransformation enzyme particularly relevant in psychiatric drugs metabolism. Therefore, characterization of its variants in Latin American population is extremely important considering that only some few studies in the region have revealed ethnic differences. Pharmacogenomics appears to be the main tool in psychiatry to select the right medicine and suitable dose for each patient

Relation of genetic variants of CYP2A6 with tobacco dependence and smoking habit in Chilean subjects. A pilot study

Background: Genetic and metabolic factors associated with nicotine metabolism may be related to smoking behavior. Aim: To assess the prevalence of allelic and genotype variants of CYP2A6 in a sample of Chilean subjects and to evaluate their relationship with smoking and tobacco dependence. Material and Methods: The genotype frequencies for *2, *3 and *4 of CYP2A6*1 (wild type) gene were determined by polymerase chain reaction (PCR) in 54 volunteers. Addiction to tobacco was evaluated using the Fagerström Test. The association between the presence of allelic variants of CYP2A6 and smoking and tobacco dependence was evaluated with chi square test. Results: The prevalence of *1, *2 (wt/*2), *3 (wt/*3 or *3/*3) and *4 (del/del) were 92.6%, 3.7%, 0% y 3.7%, respectively. No signifi cant association was observed between being a carrier of a variant genotype of CYP2A6 and smoking or tobacco dependence. Conclusions: In this sample of Chilean individuals we did not fi nd a relation between any CYP2A6 genotype with smoking or tobacco dependence.Trabajo financiado por Proyecto Departamento de Investigación y Desarrollo (DID-2000)

Biowaiver studies (in vitro) to establish equivalence of drugs

En el presente trabajo se hace un análisis de los conceptos, normativas y propuestas sobre la equivalencia terapéutica de medicamentos similares con respecto a los innovadores, desde una perspectiva internacional y nacional, explicando las bases científicas de los estudios de bioexención in vitro para determinar la intercambiabilidad de aquellos medicamentos similares provenientes de diferentes fuentes que se han liberado de los estudios de bioequivalencia (in vivo). Además, se presentan algunos resultados de estudios de test de disolución para dar a conocer la metodología usada en la bioexención y se detallan los requisitos para aprobar un Centro de Bioequivalencia in vitro

State of art of cancer pharmacogenomics in Latin American populations

Over the past decades, several studies have shown that tumor-related somatic and germline alterations predicts tumor prognosis, drug response and toxicity. Latin American populations present a vast geno-phenotypic diversity due to the great interethnic and interracial mixing. This genetic flow leads to the appearance of complex characteristics that allow individuals to adapt to endemic environments, such as high altitude or extreme tropical weather. These genetic changes, most of them subtle and unexplored, could establish a mutational profile to develop new pharmacogenomic therapies specific for Latin American populations. In this review, we present the current status of research on somatic and germline alterations in Latin America compared to those found in Caucasian and Asian populations.Latin American Society of Pharmacogenomics and Personalized Medicine (SOLFAGEM) / Fondecyt, 114043

Latin American Genes: The Great Forgotten in Rheumatoid Arthritis

The successful implementation of personalized medicine will rely on the integration of information obtained at the level of populations with the specific biological, genetic, and clinical characteristics of an individual. However, because genome-wide association studies tend to focus on populations of European descent, there is a wide gap to bridge between Caucasian and non-Caucasian populations before personalized medicine can be fully implemented, and rheumatoid arthritis (RA) is not an exception. In this review, we discuss advances in our understanding of genetic determinants of RA risk among global populations, with a focus on the Latin American population. Geographically restricted genetic diversity may have important implications for health and disease that will remain unknown until genetic association studies have been extended to include Latin American and other currently under-represented ancestries. The next few years will witness many breakthroughs in personalized medicine, including applications for common diseases and risk stratification instruments for targeted prevention/intervention strategies. Not all of these applications may be extrapolated from the Caucasian experience to Latin American or other under-represented populations.Sin financiación4.945 JCR (2020) Q1, 15/108 Health Care Sciences & Services1.254 SJR (2020) Q1, 380/2448 Medicine (miscellaneous)No data IDR 2019UE

Cytochrome P4501A1 (CYP1A1), glutathione S transferase M1 (GSTM1) polymorphisms and their association with smoking and alcohol consumption as gastric cancer susceptibility biomarkers Variantes alélicas de CYP1A1 y GSTM1 como biomarcadores de susceptibilid

Background: Gastric cancer (GaC) is the second cause of death by cancer in the world and one of the first causes in Chile. However, the burden of this disease shows remarkable worldwide variation probably explained by environmental and genetic factors. The role of susceptibility low penetrance genes and environmental and dietary factors in the etiology of gastric cancer is not well-known. Aim: To analyze the possible association between CaG susceptibility, genetic (CYP1A1 and GSTM1 polymorphisms) and environmental (tobacco and alcohol) factors. Patients and Methods: In a case-control study, we included 73 patients with a pathologically diagnosed GaC and 263 controls. DNA was extracted from peripheral blood to detect allele variants for CYP1A1 and GSTM1, using polymerase chain reactions and digestion with restriction enzymes. Results: There was a clear association of smoking and alcohol ingestion with GaC with odds ratios (OR) of 2.54 (95% confidence intervals (CI) of 1.45-4.46 and OR