Master of Science / Department of Animal Sciences and Industry / Timothy G. Rozell / Timothy G. Rozell / An increase in pre-mating dietary energy positively influences ovulation and lambing rates, and this practice is known as nutritional flushing. The mechanisms of flushing, however, are still unknown. Increasing dietary energy approximately two weeks before breeding likely increases the production of insulin-like growth factor I (IGF-I) within the ovary, which stimulates the synthesis of follicle stimulating hormone receptor (FSHR). Several alternatively spliced transcripts of the FSHR have been identified in sheep. Each variant form is believed to be produced according to the stage of follicle development. This study was carried out to evaluate expression patterns of the FSHR variant forms (FSHR-1, FSHR-2 and FSHR-3) in the sheep ovary in response to different flushing diets. For this experiment, yearling Rambouillet ewes (n=93) were allocated among 6 different energy type treatment diets, either prairie or alfalfa hay based, for at least two weeks in combination with the insertion of a controlled internal drug releasing device (CIDR). Two of the treatment groups had commercially available block supplements provided and two had rolled corn supplemented. Mid-ventral laparotomy was performed on each ewe 3.5 to 4 days after CIDR removal. Follicles 4 mm and greater were aspirated and categorized as either medium (M; 4 to 6 mm) or large (L; > 6 mm). Total RNA was extracted from granulosa cells (GC) and reverse transcribed followed by qPCR of the resulting cDNA using specifically designed primer sets for each variant of the FSHR and for the LH receptor. Changes in live weight were different (P < 0.01) between treatment diets but there were no statistical differences for NEFA concentrations between any of the treatments nor were there differences for body condition (mean = 3.0) or lambing rate. Therefore, it is likely a flushing response did not occur in this study. Expression of FSHR-1was different between M and L follicles (P < 0.01) and tended to be different for ewes fed alfalfa hay (P = 0.05). Overall mean expression of FSHR-3 was greater than expression of FSHR-1 or FSHR-2 (P < 0.01), although there was no difference between M and L follicles, or between treatment diets. The concentration of estradiol in follicular fluid was not different between the treatment diets or follicle sizes nor was expression of lutenizing hormone receptor (LHR), indicating that follicles were similar developmentally. The FSHR-1 form seemed to be the variant most likely to be involved in later stages of follicular development, and is potentially involved in follicle rescue. For all follicles, FSHR-3 was the more highly expressed form of the FSHR and may likely be essential throughout antral follicle development. Further research is required to determine the exact mechanism whereby initial energy status of ewes seems critical for the increased ovulation rate that occurs after energy supplementation (i.e. the flushing response).

The basic aim of this thesis was to evaluate the profitability of current accounts offered by the five largest Czech banks. In this context it was proposing to create such an evaluation device, which is sufficiently versatile and reusable. After a thorough examination of the general principles of decision-making theory and the basic characteristics and instruments of current accounts has been developed appropriate analytical base for follow-up of the work. In the analytical part proved very useful hierarchy of objectives and criteria, as well as the use of exact methods for determining weights of criteria and selecting the appropriate option. For determining the weights of the criteria were used point scale method, preferential ranking method, the method of paired comparisons, Saaty's method and compensation method. For the selection of variants were used multicriteria utility functions, Saaty's method and compensation method.

As fissuras orofaciais não-sindrômicas (FO-NS) correspondem a 70% de todos os casos de FO, possuem etiologia complexa e pouco compreendida, sendo consideradas de herança multifatorial com forte influência de fatores genéticos e ambientais. Apesar de estudos de análise de ligação e associação apontarem vários loci de susceptibilidade às FO-NS, o componente genético ainda não está totalmente explicado. Fatores ambientais também possuem um importante papel na etiologia das FO, e alguns já foram replicados em várias populações. Fatores como exposição materna ao álcool, drogas, tabaco, medicamentos, desnutrição e baixo nível socioeconômico são alguns dos fatores já associados a esta condição. As infecções periodontais são comuns em mulheres grávidas e estão associadas a parto prematuro, baixo peso fetal e, mais recentemente, foram reportadas como fator de risco aumentado para FO-NS nos fetos. Adicionalmente, o avanço das tecnologias de sequenciamento do DNA melhorou exponencialmente a compreensão do microbioma humano e sua influência no estado de saúde e doença, e, mais especificamente, o conhecimento sobre o impacto do microbioma na gravidez. O objetivo deste projeto foi identificar novos fatores etiológicos genéticos e ambientais das FO-NS. Para isso, primeiramente, sequenciamos 68 genes candidatos a FO por sequenciamento de nova geração em 193 indivíduos com FO-NS familial. Nós encontramos enriquecimento significativo de variantes raras e patogênicas de perda de função nos indivíduos com FO-NS e observamos que essas variantes estão em genes intolerantes a esse tipo de mutação. Também reportamos novas variantes raras do tipo perda de função no gene ARHGAP29 e sua importância na susceptibilidade as FO-NS familiais. Além disso, sugerimos o uso de um ponto de corte baseado no escore pLI do banco de dados ExAC como parâmetro para priorizar variantes em estudos de FO-NS familiares, assumindo modelo de herança mono ou oligogênico. Adicionalmente, estudamos o microbioma oral de mães de crianças com FO-NS e mães de crianças sem malformações, utilizando o sequenciamento da subunidade 16S do rRNA das bactérias com o objetivo de verificar diferenças consistentes na composição do microbioma oral de mães de crianças com FO-NS, levando em consideração a presença ou não de doenças infecciosas periodontais maternas. A casuística foi composta de 6 mães de recém-nascidos de até 1 mês que apresentaram FO-NS ao nascimento e mães de crianças sem qualquer malformação congênita. As análises de alfa e beta diversidades não demonstraram diferença significativa na composição do microbioma oral de mães de crianças com FO-NS e mães de crianças controle, contudo observamos que o grupo com infecções periodontais possui a diversidade taxonômica mais abundante do que o grupo hígido. Em resumo, nesse estudo piloto não foi possível identificar alterações no microbioma oral como um fator etiológico das FO-NS. Novas análises em uma casuística maior são necessárias para a confirmação desse achado / The non-syndromic orofacial clefts (nsOFC) correspond to 70% of all OFC cases, have complex etiology and are poorly understood, being considered multifactorial inheritance with a strong influence of genetic and environmental factors. Although linkage and association analysis studies point to several nsOFC susceptibility loci, the genetic component is not yet fully explained. Environmental factors also play an important role in OFC etiology, and some have been replicated in several populations. Factors such as maternal exposure to alcohol, drugs, tobacco, drugs, malnutrition and low socioeconomic status are some of the factors already associated with this condition. Periodontal infections are common in pregnant women and are associated with preterm birth, low birth weight and, more recently, have been reported as an increased risk factor for nsOFC in fetuses. Additionally, the advancement of DNA sequencing technologies has exponentially improved the understanding of the human microbiome and its influence on health and disease status, and, more specifically, knowledge about the impact of the microbiome on pregnancy. The objective of this project was to identify new genetic and environmental etiological factors of nsOFC. For this, we first sequenced 68 candidate genes by next generation sequencing in 193 individuals with familial nsOFC. We found significant enrichment of rare and pathogenic loss of function variants in individuals with nsOFC and we observed that these variants were in genes intolerant to this type of mutation. We also reported new rare loss-of-function variants in the ARHGAP29 gene and its importance in the liability of familial nsOFC. In addition, we suggested the use of a cutoff point based on the ExAC database pLI score as a parameter to prioritize variants in familial nsOFC studies, assuming a mono or oligogenic inheritance model. In addition, we studied the oral microbiome of 6 mothers of newborns up to 1-month-old with nsOFC and 6 mothers of newborns without congenital malformations using the 16S rRNA sequencing in order to verify consistent differences in the composition of the oral microbiome of mothers of children with nsOFC, taking into account the presence or absence of maternal periodontal infectious diseases. The analysis of alpha and beta diversities did not show a significant difference in the composition of the oral microbiome of mothers of nsOFC children and mothers of control children, however, we observed that the group with periodontal infectious diseases has more abundant taxonomic diversity than the healthy group. In summary, in this pilot study, it was not possible to identify alterations in the oral microbiome as an etiological factor of FO-NS. New analyzes in a larger cohort are necessary to confirm this finding

Esta pesquisa tem como objetivos: a) reproduzir o manuscrito Diario da Navegaçaõ de Theotonio Joze Juzarte (testemunho do museu paulista/Ipiranga) com as edições fac-similar e paleográfica, justalinearmente; b) apontar as variantes semântico-sintáticas e semânticolexicais da edição Uspiana Brasil 500 anos em relação ao manuscrito supracitado; e da cópia em Portugal (Biblioteca Nacional de Portugal) em relação ao documento no Brasil. Para atingir tais objetivos, orientou-se pelos preceitos teórico-metodológicos da Crítica Textual em Cambraia (2005) e Spina (1997); adentrou-se no contexto histórico; fizeram-se as análises codicológica e paleográfica, sucintamente; escanearam-se fotos; digitalizou-se todo o manuscrito, conforme as regras da edição paleográfica; fez-se o levantamento das variantes que interferem no sentido do texto manuscrito do Brasil, comentando-as. Essas variantes ocorreram, principalmente, por omissão ou por substituição de grafemas, palavras, sintagmas e frases erros de leitura do modelo (paleográficos); de memorização (retenção do texto), de ditado interior. A pesquisa revelou uma série de variantes (semântico-sintáticas e semânticolexicais) que possibilitaram uma diversidade de comentários, comprovando que ainda há dificuldades na elaboração de edições, no Brasil. / This research aims to: a) reproduce the manuscript Diario de navegação of Theotonio Joze Juzarte with facsimile and paleographic editions, line by line; b) point out the semanticsyntactic and semantic-lexical variants of the Uspiana Brasil 500 anos issue as related to the above manuscript, and the copy in Portugal (Biblioteca Nacional de Portugal) relative to the document in Brazil. To achieve these objectives, guided by the theoretical and methodological principles of textual criticism - in Cambraia (2005) and Spina (1997), the historical context was investigated; the codicological and paleographic analysis was briefly proceeded; pictures were scanned; the whole manuscript was scanned, according to the paleographic rules edition; the survey of the variants that affect the meaning of the text in Brazil was performed and commentated. These variants occur mostly by omission or by substitution of graphemes, words, syntagms, and phrases - model reading errors (paleographic); memorization (text retention) of prior dictation. The research revealed a number of variants (semantic, syntactic, and semantic-lexical) that enabled a variety of comments, proving that rigor is still missing in the preparation of editions in Brazil.

Les affections cardiovasculaires sont des pathologies complexes résultant des interconnexions d'un grand nombre de facteurs de risque. Si l'étiologie génétique de ces affections a largement été étudiée, les variants fonctionnels à l'origine de la large héritabilité génétique des facteurs de risque cardiovasculaire et les mécanismes d'interactions gène-gène-environnement masquant ou modulant l'effet de la génétique restent à élucider.Ce mémoire présente l'étude de la génétique de facteurs de risque des pathologies cardiovasculaires : les lipides, la pression artérielle, l'haptoglobine et le facteur de croissance de l'endothélium vasculaire.Nous avons réalisé des études d'association pangénomique sur 631 enfants non apparentés issus de la cohorte STANISLAS et avons répliqué nos résultats sur près de 9 000 enfants appartenant à quatre cohortes pédiatriques et 13 300 adultes provenant de trois cohortes distinctes.Nous avons ainsi pu démontrer que certaines associations génétiques mises en évidence chez l'adulte avaient un effet observable dès l'enfance et avons discuté des outils bioinformatiques, biostatistiques et méthodologiques manquants encore aujourd'hui à l'approche pangénomique ; notamment l'intérêt des approches transcriptomiques en validation.En conclusion, lors de notre thèse, nous avons eu à la fois une démarche épidémiologique et une démarche de proposition de designs intégrés permettant de mener plus avant les investigations sur l'étiologie génétique des pathologies cardiovasculaires / Complex synergies of multiple risk factors are at the origin of cardiovascular pathologies. Their genetic etiology has been extensively investigated but many questions remain on the identification of functional variants explaining the large genetic heritability of cardiovascular risk factors and gene-gene-environment interactions hiding or modulating genetics underpinning cardiovascular physiopathology.Herein we describe our study of the genetics of cardiovascular risk factors: lipids, blood pressure, haptoglobin and vascular endothelial growth factor.We performed Genome-Wide Scan Association Studies (GWAS) on a subsample of 631 unrelated children selected in the STANISLAS cohort and replicated our results in 9,000 children from four pediatric cohorts and 13,300 adults from three different cohorts.We demonstrated that genetic associations highlighted in adults were observable in childhood and addressed the tools missing in bioinformatics, biostatistics and methodologies used in GWAS approaches, notably concerning trasncriptomic validations.In summary, during our thesis, we followed an epidemiologic approach and proposed integrated designs in order to upgrade the investigations on genetic epidemiology of cardiovascular diseases

La maladie de Crohn est présente principalement dans les pays industrialisés. En France, elle touche 1 personne sur 1000. L’incidence est de 5 pour 100000 habitants par an. A l’heure actuelle sa pathogénie reste mal expliquée et de nombreux facteurs interviennent (facteurs génétiques, immunologiques et environnementaux). Il semble donc essentiel de mieux comprendre la pathogénie de la maladie de Crohn afin d’identifier des cibles thérapeutiques permettant d’améliorer sa prise en charge et d’identifier des facteurs prédictifs de la récidive post-opératoire et des complications post-opératoires afin de personnaliser la prise en charge de chaque patient. Dans ce travail nous avons montré qu'un variant génétique de CARD8 (rs2043211) est un facteur de risque de récidive post-opératoire. Cette association n’est pas influencée par les autres facteurs de risque connus comme le tabagisme actif. L’identification de CARD8 comme un facteur de risque génétique de risque de récidive chirurgicale est d’un intérêt particulier puisqu’il pourrait devenir une nouvelle cible thérapeutique pour le traitement de la maladie de Crohn dans la période post-opératoire. Notre travail a également montré qu'un variant génétique de NOD2 (rs5743289) est un facteur de risque de complications intra-abdominales infectieuses post-opératoires (CIIP) après chirurgie dans la maladie de Crohn. L’identification de NOD2 comme un gène à risque pour la survenue de CIIP pourrait permettre d’établir une stratification précoce des patients à haut risque de CIIP chez qui la chirurgie devra être planifiée et prédire les patients à haut risque de CIIP. Des études sur larges effectifs avec cohorte de réplication restent encore nécessaires avant que les patients puissent bénéficier des retombées de ces outils en pratique courante / Crohn's disease occurs mainly in industrialized countries. In France it affects 1 person in 1000. The incidence is 5 per 100,000 persons per year. At present its pathogenesis remains poorly explained and many factors are involved (genetic, immunological and environmental). It seems essential to better understand Crohn's disease pathogenesis in order to identify therapeutic targets to improve its management and to identify predictors of postoperative recurrence and postoperative complications to customize the care of each patient. In this work we showed that a genetic variant of CARD8 (rs2043211) is a risk factor for postoperative recurrence. This combination is not influenced by the other known risk factors such as active smoking. Identifying CARD8 as a genetic risk factor for risk of surgical recurrence is of particular interest since it may become a novel therapeutic target for the treatment of Crohn's disease in the post-operative period. Our work has also shown that a genetic variant of NOD2 (rs5743289) is a risk factor for postoperative intraabdominal infectious complications (CIIP) after surgery in Crohn's disease. The identification of NOD2 gene as a risk factor for the occurrence of CIIP could establish an early stratification of patients at high risk for CIIP in whom surgery should be planned and predict patients at high risk for CIIP. Studies with large numbers replication cohort are still necessary before patients can enjoy the benefits of these tools in clinical practice

Decision making is an inherent part of human life. Every day we decide on little things, but also some more complex problems may appear. In such cases, we need to choose a more complex process leading to the final decision. To do so, many multiple-criteria decision-making methods can be used. These methods will be explored in this thesis. They will be used to select accident insurance according to the preferences and requirements of several respondents. Accident insurance protects the insured person against the impairment of their life caused by the consequences of their injury. Accident insurance is a commitment for many years, so its choice needs close attention. The choice of the insurance can be assessed based on of several criteria. Designing a model of multi-criteria decision-making strategy was the main goal of this diploma thesis. The thesis is divided into two parts - the theoretical and practical part. Theoretical part defines the concepts of decision making, multi-criteria decision making and its methods using specialized literature. It also defines the concept of insurance and its specifics relating to accident insurance. The practical part focuses on the specific solution of the given problem. The first step was a survey of offers of insurance companies operating on the Czech market that have separate accident insurance in their product portfolio. Based on these offers, decision variants have been created. The second step was to determine the five criteria on whose basis the variants were evaluated. After the general procedure has been established, the model has been applied. The proposed procedure was tried on a group of respondents to select the best offer for them. The target group, for which the procedure was designed, was set for people between the ages of 40 and 50 who do not have a risky job and do not engage in any hazardous leisure activities. Their preferences were determined by a questionnaire, based on which the decision matrices and weightings of the individual criteria were compiled. The optimal option was recommended to respondents.

Este trabalho compõe o projeto \"Formação e expansão do português paulista ao longo do Rio Tietê a partir do séc. XVII\", sendo um subprojeto do Projeto Caipira, que está desenvolvendo pesquisas relacionadas à comunidade linguística de São Paulo por pessoal ligado basicamente ao Departamento de Letras Clássicas e Vernáculas da USP. Dentre as cidades estudadas está a região de Capivari, situada a 108 quilômetros de São Paulo, cidade do imortal Amadeu Amaral, autor da obra O Dialeto Caipira (1920), primeiro estudo a preocupar-se com a diversidade do falar paulista. Esta dissertação tem como proposta a busca exaustiva de variantes fonéticas em documentos cartoriais do século XIX, de modo a expressar (ou não) os estudos dialetais feitos pelo autor em questão, demonstrando o que já pertencia à língua antes de suas observações, pois os fólios datam de anos anteriores ao seu nascimento. Embora sejam documentos que, por serem escritos por pessoas supostamente alfabetizadas, hipoteticamente podem denotar a norma culta escrita de então, é possível encontrar neles características dialetais apontadas por Amaral, como veremos. Para contemplar o estudo sobre a linguagem atual da região, também se realizou um breve exame do falar dos capivarianos, cotejando a locução atual com as variantes registradas nos fólios e mostrando, assim, o que permaneceu no dialeto após quase um século da publicação do livro. Sendo um trabalho comparativo, seguiremos o caminho feito por Amaral (1920) em seu capítulo sobre Fonética: falaremos da generalidade do falar dos habitantes, dos fonemas e suas alterações normais, das vogais, grupos vocálicos, consoantes e modificações isoladas. Assim, o trabalho objetiva mostrar que muitos dos fenômenos linguísticos que observamos atualmente no português também podem ser vistos registrados em fases anteriores da língua, como comprova os documentos do século XIX, e embora nossa língua mude, ainda guarda muitos traços de nossos antepassados. E ainda, apesar de o estudo ter sido feito tomando a cidade de Capivari e a obra de Amadeu Amaral como guia, ele também representa a realidade de muitas outras cidades de São Paulo e do Brasil, as quais mantêm em seus dialetos locais os apontamentos vistos aqui. / This essay belongs to Formation and Expansion of Paulista Portuguese through Tietê river since 19th century project, and it is also a subproject of Caipira Project, which is developing researches in the linguistic community in São Paulo by people of the Department of Classic and Vernaculars Letters of USP. Capivari is among the studied cities and it is located 108 kilometers from São Paulo, city of the Immortal Amadeu Amaral, author of the book O Dialeto Caipira (The Caipira Dialect), 1920 first study of the paulista speaking diversity this essay does an exhaustive searching for phonetic variants on register officers documents from 19th century in order to show (or not) the dialect studies made by the author, demonstrating elements that belonged to idiom after his observations, because the folios are very antique. Although the documents were written by persons supposedly literate, hypothetically they may denote the cultural norms of writing and you can find them dialects characteristics identified by Amaral, as we shall see. To complete the study about the language nowadays, it was done a brief exam of capivariano speak, comparing the actual locution to registered variants on the folios to show what has continued in the dialect before around one century of the book publication. Being a comparative dissertation, the essay was followed the chapter about Phonetic of Amarals book (1920): we talk about the generality of the capivariano speak, phonemes and its normal modifications, vowels, vowel groups, consonants and disconnected variations. Thus, the study aims to show that many linguistic phenomena that we observe today in Portuguese can also be seen recorded in previous stages of language justified on the 19th century documents and, even though our language is developing, it is keeping many characteristics of our ancestors. And although the research had seen done in Capivary and following Amadeu Amarals book, the studies show the reality of many São Paulo and Brazil cities, which have many observations in their dialects that were showed here.

Iguape é um dos municípios do litoral sul paulista que teve muita importância na história do Brasil Colonial. Conheceu o auge com o ciclo do arroz, quando o rio Ribeira de Iguape era o principal meio de transporte e o porto às suas margens um dos mais importantes do País. Depois veio o declínio, conseqüência da abertura do Valo Grande e do assoreamento de seu porto. E, por fim, veio o isolamento numa das regiões mais pobres do Estado de São Paulo, o Vale do Ribeira. Iguape é o ponto 334 indicado por Antenor Nascentes para a pesquisa da realidade dialetal brasileira. O presente estudo objetiva registrar amostras desse verdadeiro dialeto caiçara, bolsão de tupinismos, arcaísmos e variantes lexicais peculiares. Procurou-se arrolar as lexias mais utilizadas na região não somente para lançá-las num mapa. Além de fazer o tratamento quantitativo dos dados, com o apoio das noções de estatística lexical de Muller, privilegiou-se a abordagem dos aspectos semântico-lexicais, com base em Pottier e Rastier, partindo da concepção de norma de Coseriu. Com base nos procedimentos teórico-metodológicos da Geolingüística da atualidade, aplicaram-se as questões da área Corpo Humano do Questionário semântico-lexical do Projeto ALiB, versão 2001, em três pontos do município de Iguape Icapara, Rocio e Jairê, a doze sujeitos, quatro de cada ponto, dos dois gêneros e em duas faixas etárias, quais sejam, de 18 a 30 anos (primeira faixa) e de 66 anos em diante (segunda faixa). A partir das respostas obtidas nas entrevistas, elaboraram-se dezesseis cartogramas, que espelham a variação diatópica de cunho lexical. Ainda em consonância com os preceitos da Geolingüística moderna, que alia sua metodologia às da Sociolingüística, compondo um quadro pluridimensional, mostrou-se o quadro da diversidade lingüística local. Em suma, o trabalho faz o registro da realidade lingüística desta parte muito pequena do Brasil, mas de grande importância para os estudos geolingüísticos, antes que esses falares se percam, quer pela ação homogeneizadora dos meios de comunicação de massa, quer pelas próprias forças centrífugas da língua. / Iguape is one of the cities on the southern coast of São Paulo State that had great importance in the History of colonial Brazil. It had its days of glory during the rice plantation period, when Ribeira de Iguape River was the main means of transportation and the port on its banks was one of the most important in the country. Later, decline came as a consequence of the opening of Valo Grande and the aggradation of its port. Finally, it became isolated in one of the poorest areas of the São Paulo State, the Ribeira Valley. Iguape is point number 334, as indicated by Antenor Nascentes, for the research of the Brazilian dialectal reality. The present work aims at registering samples of this truly \"caiçara\" dialect, in a region of \"tupinisms\", archaisms and peculiar lexical variants. We intended not only to place the lexias used in the area on a map, but also to list the most frequent ones. Besides doing quantitative treatment to data, based on Muller\'s notions of Lexical Statistics, we have focused in approaching the semantic-lexical aspects, based on Pottier and Rastier and starting from Coseriu\'s notion of norm. Based on present Geolinguistics theoretical-methodological procedures, we have applied the questions from area \"Human Body\" in the semantic-lexical Questionnaire of Project AliB, version 2001, in three points of the city of Iguape - namely Icapara, Rocio e Jairê -, to twelve subjects, four in each point, from both genders and belonging to two age groups, between 18 to 30 (first group) and older than 66 (second group). From the answers obtained in interviews, we have elaborated sixteen cartograms, which reflect the diatopic variation on lexical basis. Still in consonance with the principles of modern Geolinguistics, which allies its methodology to the one used in Sociolinguistics, forming a pluridimensional framework, we have showed the picture of local linguistic diversity. In summary, this work registers the linguistic reality of this very small part of Brazil, which has great importance to geolinguistic studies, before the loss of these speeches, be it by the homogenizing effect of mass media or by language\'s own centrifugal forces.

Made available in DSpace on 2016-08-10T10:39:16Z (GMT). No. of bitstreams: 1 NURIA ALONSO LOPEZ CID.pdf: 1461437 bytes, checksum: 7aabd2e9fb0164bdf7480906eadb35b7 (MD5) Previous issue date: 2016-04-14 / The advances in Anesthesiology took place at the same time as the development of drugs that ensured greater control over pain, patient comfort, and safety during surgical anesthetic procedures. Pharmacogenetics is the science that enables enhanced healthcare, by understanding the genetic variations that may affect the different responses to treatments. CYP3A are the most important enzymes involved in the metabolism of drugs prescribed in clinical practice, showing extensive genetic variability in their expression. CYP3A5 presents the highest number of functional variants, with significant differences in the frequencies observed among different population groups around the world and in Brazil. This study aimed and at assessing the frequency of CYP3A5*3 and CYP3A5*6 genotypic and allelic variants and to estimate the metabolizing profile according to these variants, as well as any potential implications on adverse events with drugs used in anesthesia. The sample used for this study included 166 subjects users of the Laboratório da Área de Saúde da PUCGoiás (PUC Healthcare Laboratory city of Goiás). They were all born in the Brazilian Midwest, over 18 years of age, and from both genders. The blood samples were obtained from each individual and genotyped for CYP3A5*3, A>G (rs 776746) and CYP3A5*6, G>A (rs 10264272) by real time Polymerase Chain Reaction using TaqMan assays. Data analysis of the allelic frequency was conducted by calculating the percentage for the established groups, according to color or race, compared to the total sample. In individuals from the Brazilian Midwest, assessed in this study, the frequency of the allelic variant CYP3A5*3 was 40% and 2% for CYP3A5*6. The frequency observed for the CYP3A5*3 allelic variant in subjects from the Midwest was lower than that from other Brazilian studies and also lower than the frequencies observed in Europeans and Asians, however, they were similar to the frequency seen in populations from East and West Africa. The frequency of the CYP3A5*6 allelic variant, in this study, was higher than that found in European studies and similar of the subjects in the North of Africa. Based on the results, one may infer that 72% would be poor metabolizers. The higher frequency of the poor metabolizer profile shows that there is potential for a greater occurrence of adverse events when using drugs metabolized by CYP3A5 in this population from the Brazilian Midwest. / O progresso da Anestesiologia junto com o desenvolvimento de drogas garantiram maior controle da dor, conforto ao paciente e segurança durante o ato anestésicocirúrgico. A Farmacogenética é uma ciência que permite a melhora da assistência à saúde, por meio do conhecimento das variações genéticas que podem estar envolvidas com as diferenças na resposta terapêutica. As CYP3A são as enzimas mais importantes envolvidas com o metabolismo de drogas prescritas na prática clínica, apresentando grande variabilidade genética na sua expressão. A CYP3A5 é a forma que apresenta mais variantes funcionais e com diferenças expressivas nas frequências observadas em diferentes grupos populacionais do mundo. Este estudo teve como objetivo avaliar a frequência das variantes genotípicas e alélicas do CYP3A5*3 e CYP3A5*6 e inferir sobre o perfil metabolizador dos indivíduos em função destas variantes em relação a drogas usadas em anestesia. O grupo avaliado incluiu 166 indivíduos usuários do Laboratório da Área de Saúde da PUCGoiás, nascidos na região Centro-Oeste do Brasil, maiores de 18 anos e de ambos os sexos. As amostras de sangue foram obtidas de cada indivíduo e genotipados para CYP3A5*3, A>G (rs 776746) and CYP3A5*6, G>A (rs 10264272) por Reação em Cadeia de Polimerase usando sondas TaqMan. A análise dos dados das frequências alélicas foi realizada através do cálculo das porcentagens para os grupos estabelecidos, segundo a cor ou raça, em relação a amostra total. Nos indivíduos da região Centro-Oeste do Brasil avaliados neste estudo, a frequência da variante alélica CYP3A5*3 foi de 40% e da CYP3A5*6 foi de 2%. A frequência observada para a variante alélica CYP3A5*3 em indivíduos da região Centro-Oeste foi menor que a de outros estudos brasileiros e também menor que as frequências verificadas em europeus e asiáticos, porém similar à observada na população do leste e oeste da África. A frequência da variante alélica CYP3A5*6, neste estudo, foi maior que a encontrada em estudos europeus e com valores mais próximos daqueles observados no norte da África. Com base nos resultados obtidos da amostra pode-se inferir que 72% dos indivíduos seriam fracos metabolizadores. A maior frequência do perfil de fraco metabolizador mostra que existe potencial de maior ocorrência de eventos adversos no uso de fármacos metabolizados pela CYP3A5 nesta população da região Centro-Oeste do Brasil.