Genetic polymorphisms in external apical root resorption and orthodontic tooth movements: A systematic review.

Objective: External apical root resorption (EARR) is characterized by permanent loss of dental structure at the root apex. This study aimed to systematically review gene polymorphisms associated with EARR in orthodontic patients. Methods: Electronic database searches were performed across several databases. Results: This systematic review included 21 studies. Outcome measures were based on tooth dimensions observed on radiographs obtained before and after treatment. Polymorphisms in the following genes were genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis: purinergic-receptor-P2X, ligand-gated ion channel 7 (P2RX7), caspase-1/interleukin-converting enzyme (CASP1/ICE), caspase-5 (CASP5), IL-1beta (IL1B), IL-1alpha (IL1A), interleukin-1 receptor antagonist gene (IL1RN), tissue non-specific alkaline phosphatase (TNSALP), tumor necrosis factor-alpha (TNFα), tumor necrosis factor receptor superfamily gene member 11a (TNFRSF11A), secreted phosphoprotein 1 (SPP1), tumor necrosis factor receptor superfamily gene member 11b (TNFRSF11B), interleukin 17A (IL17), interleukin 6 (IL6), receptor activator of nuclear factor-kappa B (RANK), osteoprotegerin (OPG), stromal antigen 2 (STAG2), vitamin D receptor (VDR), cytochrome P450 family 24 subfamily A member 1 (CYP24A1), cytochrome P450 family 27 subfamily B (CYP27B1), group-specific component (GC), and interleukin-1 receptor-associated kinases 1 (IRAK1). Conclusions: Almost all studies suggested that IL1 gene is associated with EARR. Additionally, P2RX7 may be an important factor contributing to the etiopathogenesis of EARR. TNFRSF11A, SPP1, IL1RN, IL6, TNFRSF11B, STAG2, VDR, IRAK1, IL-17, CASP1/ICE and CASP5 have been identified in isolated studies. Further observational studies are needed to better explain the association between these genes and EARR.

Exploring the molecular pathways linking sleep phenotypes and POGZ-associated neurodevelopmental disorder.

Pogo transposable element-derived protein with ZNF domain (POGZ) gene encodes a chromatin regulator and rare variants on this gene have been associated with a broad spectrum of neurodevelopmental disorders, such as White-Sutton syndrome. Patient clinical manifestations frequently include developmental delay, autism spectrum disorder and obesity. Sleep disturbances are also commonly observed in these patients, yet the biological pathways which link sleep traits to the POGZ-associated syndrome remain unclear. We screened for sleep implications among individuals with causative POGZ variants previously described. Sleep disturbances were observed in 52% of patients, and being obese was not observed as a risk factor for sleep problems. Next, we identified genes associated with sleep-associated traits among the POGZ regulatory targets, aiming to uncover the molecular pathways that, when disrupted by POGZ loss of function, contribute to the aetiology of sleep phenotypes in these patients. The intersect between POGZ targets and sleep-related genes was used in a pathway enrichment analysis. Relevant pathways among these overlapping genes are involved in the regulation of circadian rhythm, tau protein binding, ATPase activator activity. This study may represent the beginning for novel functional investigations on shared molecular mechanisms between sleep disturbances and rare developmental syndromes related to POGZ and its regulatory targets.

Aspectos éticos y recomendaciones para investigación en seres humanos en la era genómica / Ethical aspects and recommendations for human research in the genomic age

Este artículo revisa los principales desafíos éticos que plantea la investigación vinculada al genoma humano a la luz de la bibliografía internacional y entrega recomendaciones sobre su abordaje basada en nuestra experiencia en el Comité de Ética para la Investigación en Seres Humanos de la Facultad de Medicina, Universidad de Chile, incluyendo las regulaciones legales nacionales. Los estándares éticos de la investigación en seres humanos deben extremarse para proteger adecuadamente a los participantes en estudios involucrados con la genómica. Especialmente relevantes en este contexto son: la protección de la confidencialidad y anonimato; la política de entrega de resultados y la posibilidad de retirarse del estudio. Compartir datos resultantes de investigaciones genéticas permite optimizar recursos, otorga mayor transparencia y replicabilidad de los análisis y permite descubrir alteraciones genéticas responsables de enfermedades raras y genes involucrados en enfermedades hereditarias multifactoriales, además de contribuir al diseño de medicina de precisión y de nuevas estrategias terapéuticas. Sin embargo, plantea grandes desafíos: proteger la privacidad y evitar la re-identificación de los voluntarios, la entrega de resultados con asesoría pre y post estudio. Estos aspectos requieren la elaboración de un cuidadoso proceso de consentimiento informado para investigaciones genómicas cuyos componentes principales se analizan en este artículo.

This article reviews the main ethical challenges posed by human genome research in the light of the international literature and provides recommendations on how to approach them based on our experience in the Ethics Committee for Research on Human Subjects of the Faculty of Medicine, University of Chile, including national legal regulations. Ethical standards in human research must be extreme, in order to adequately protect participants in studies involving genomics. Particularly relevant in this context are the protection of confidentiality and anonymity; the policy of delivery of results and the possibility of withdrawing from the study. Sharing data resulting from genetic research optimizes resources, provides greater transparency, and replicability of the analyses and makes it possible to discover genetic alterations responsible for rare diseases and genes involved in multi-factorial hereditary diseases, as well as contributing to the design of precision medicine and new therapeutic strategies. However, it poses great challenges: protecting privacy and avoiding re-identification of volunteers, delivery of results with pre- and post-study counseling. These aspects require the elaboration of a careful informed consent process for genomic research, the main components of which are discussed in this article.

Attitudes Toward Psychiatric Genetic Testing and Research: A Comparative Study Between Denmark and Cuba.

Introduction: Psychiatric genetic research has seen progress in identifying genetic risk variants associated with major mental disorders. Testing with preventive purposes is likely to be offered to high-risk individuals in the near future. It is important that genetic testing and counseling align with the interests of the patients, and these interests are likely to vary among countries and cultures. Aim: The present study aimed to compare the attitudes toward psychiatric genetic research and genetic testing in Denmark and Cuba. Materials and Methods: A survey, culturally adapted for each country, was administered to a pool of students, patients with depression, and the closest relatives of these patients. A total of 491 stakeholders from Denmark and 720 from Cuba were included in the study. Results: Significant differences between the two populations were found for general knowledge about psychiatric genetic research, whom to offer genetic testing, and to whom to entrust with psychiatric genetic information. Cuban stakeholders were more likely to feel uncomfortable about psychiatric genetic research than the Danish stakeholders. This difference might be driven by the characteristics of the health systems, sociocultural factors, and lower genetic literacy in the Cuban population. Conclusion: This study is the first to compare attitudes toward psychiatric genetic testing between a Latin American country and a Nordic country. The results reported could be valuable when designing general guidelines for psychiatric genetic testing in the future.

Diseños de investigación en epidemiología genética / Genetic epidemiology research designs

Se describen los distintivos de los diseños de investigación epidemiológica que son utilizados con mayor frecuencia en los estudios de asociación genética. Los estudios de casos y controles proporcionan un método eficiente para evaluar asociaciones entre genes candidatos y enfermedad. Los estudios de cohorte, por su parte, si bien aportan un mayor grado de causalidad, no son eficientes para la exploración inicial en la identificación de las asociaciones gen-enfermedad. Los estudios transversales son menos costosos, requieren períodos de tiempo más cortos y son de utilidad para estimar la prevalencia de enfermedades, de factores de riesgo o de variantes genéticas. Los estudios basados en familias han sido exitosos para encontrar alelos que confieren mayor riesgo para el desarrollo de enfermedades de transmisión mendeliana.

This article describes the features of the epidemiologic research designs most commonly used in genetic association studies. Case-control studies are efficient in evaluating associations between candidate genes and disease. Cohort studies, in contrast, yield a greater degree of causality but are not efficient for the initial exploration to identify gene-disease associations. Cross-sectional studies are less expensive, require less time, and are useful for estimating the prevalence of diseases, risk factors, and genetic variants. Family-based studies have been successful in finding alleles that confer greater risk for developing Mendelian inheritance disorders.

A review of psychiatric genetics research in the Brazilian population / Uma revisão sobre a pesquisa genética psiquiátrica na população brasileira

OBJECTIVE AND METHOD: A large increase in the number of Brazilian studies on psychiatric genetics has been observed in the 1970's since the first publications conducted by a group of researchers in Brazil. Here we reviewed the literature and evaluated the advantages and difficulties of psychiatric genetic studies in the Brazilian population. CONCLUSION: The Brazilian population is one of the most heterogeneous populations in the world, formed mainly by the admixture between European, African and Native American populations. Although the admixture process is not a particularity of the Brazilian population, much of the history and social development in Brazil underlies the ethnic melting pot we observe nowadays. Such ethnical heterogeneity of the Brazilian population obviously brings some problems when performing genetic studies. However, the Brazilian population offers a number of particular characteristics that are of major interest when genetic studies are carried out, such as the presence of isolated populations. Thus, differences in the genetic profile and in the exposure to environmental risks may result in different interactions and pathways to psychopathology.

OBJETIVO E MÉTODO: Desde a década de 70, quando os primeiros estudos em genética psiquiátrica conduzidos por um grupo de brasileiros foram publicados, o número de trabalhos realizados no Brasil vem aumentando consideravelmente. Através desta revisão, avaliamos as vantagens e as dificuldades da realização de pesquisas em psiquiatria genética na população brasileira. CONCLUSÃO: A população brasileira é uma das mais heterogêneas do mundo, formada principalmente pela combinação entre populações européia, africana e nativa americana. Apesar de a mistura entre raças não ser uma particularidade da população brasileira, a história e o desenvolvimento social no Brasil ocasionou uma grande miscigenação étnica, a qual é observada atualmente. Devido à heterogeneidade de suas origens, diversos problemas são levantados em estudos genéticos realizados no Brasil. Porém, a população brasileira oferece características particulares para desenvolvimento de pesquisas genéticas, como a presença de populações isoladas. Portanto, diferenças genéticas e exposição a riscos ambientais podem resultar em diferentes interações e caminhos para alterações psicopatológicas.

Os riscos genômicos e a responsabilidade pessoal em saúde / Genomic risk and personal responsibility in health

With the advent of genomic research, a new category of risk has emerged-genetic risk-from which an individual cannot be separated. Among the outcomes of this model is a discussion on personal accountability, according to which an individual may both be exempted from events related to certain states of health ("blame it on the genes") or be blamed for those events ("transmitter of disease"). In addition, the search for genes to explain disease erases the line between what is normal and what is pathological, with a growing tendency towards considering individuals with no or very mild clinical manifestations as being "ill." The great emphasis on genomics may lead to both an exaggerated attention to genetics rather than social and environmental factors and to a reductionism that favors sociobiological explanations for human behavior. In addition, in this scenario, the right to information may paradoxically stimulate some to consume goods and services in order to prevent a hypothetical illness that could occur at some point in time as a result of genetic predisposition-goods and services that may not be available to everyone. It is essential that such issues be considered with the same urgency with which the genomic paradigm is being developed.

O risco familiar de câncer de mama: a psicanálise diante da pesquisa genética

A Pesquisa Genética está definitivamente na pauta da ciência deste século. Em poucas ocasiões, porém, foi analisada sob a ótica da psicanálise. Este trabalho assume a perspectiva de abordar o risco familiar de câncer de mama pelo viés psicanalítico. Para tal, avalia a posição de quatro mulheres que se submeteram à pesquisa genética desenvolvida, em nível regional, pelo Instituto da Mama do Rio Grande do Sul, vinculado ao Banco Nacional de DNA, com o intuito de verificar a ocorrência de mutação genética responsável pelo câncer de mama hereditário. Aborda as influências tecnológicas na subjetividade e a posição do sujeito frente à hereditariedade, à herança e à enfermidade. Este trabalho de pesquisa é parte de um estudo denominado “Estudo psicanalítico do adoecer de câncer de mama” que , por sua vez fez parte do projeto mais amplo designado como Projeto do Banco Nacional de DNA, executado junto ao Ministério da Saúde.

La Investigación Genética es indudablemente un tema científico relevante de este siglo. No obstante, en muy pocas ocasiones fue analizada bajo la óptica del psicoanálisis. Este trabajo adopta la perspectiva de abordar el riesgo familiar de cáncer de mama desde un perfil psicoanalítico. Con esa finalidad, evalúa la posición de cuatro mujeres que se sometieron a la indagación genética llevada a cabo, a nivel regional, por el Instituto da Mama do Rio Grande do Sul, vinculado al Banco Nacional de DNA, con el objeto de verificar la ocurrencia de la mutación genética, responsable por el cáncer de mama hereditario. Aborda las influencias tecnológicas en la subjetividad y en la posición del sujeto frente a la enfermedad hereditaria, la herencia y la enfermedad. Este trabajo de investigación es parte de un estudio denominado “Estudio Psicoanalítico de la Enfermedad de Cáncer de Mama”, que a su vez forma parte de un proyecto más amplio llamado Projeto do Banco Nacional de DNA, realizado conjuntamente con el Ministério de Salud.

La recherche génétique est définitivement à l’ordre du jour pour la science de ce siècle. Cependant, elle a rarement été analysée dans la perspective de la psychanalyse. Ce travail aborde le risque héréditaire de cancer du sein à travers un regard psychanalytique. Pour ce faire, il évalue la place de quatre femmes ayant participé à la recherche génétique développée au niveau régional par l´Institut du Sein de l’état du Rio Grande do Sul, rattaché à la Banque Nationale d’ADN, dans l’objectif de vérifier la survenue de mutation génétique responsable du cancer héréditaire du sein. Il aborde les influences technologiques sur la subjectivité et la position du sujet face à l´héréditaire et la maladie. Ce travail de recherche fait partie d’une étude intitulée “Étude Psychanalytique sur l’apparition du cancer du sein”, qui pour sa part, fait partie d´un projet plus vaste, le Projet de la Banque Nationale d’ADN, réalisé conjointement avec le Ministère de la Santé.

Genetic research is clearly a relevant scientific issue in this century. On very few occasions, however, has it been analysed from a psychoanalytical perspective. This paper discusses the family-related risk of breast cancer from a psychoanalytical approach. The positions of four women who underwent genetic research are evaluated, based on a regional study carried out by the Instituto da Mama do Rio Grande do Sul, associated with the Banco Nacional de DNA with the purpose of verifying the occurrence of the genetic mutation responsible for the heredity of breast cancer. The paper discusses the technological influences on subjectivity and the position concerning heredity, inheritance and illness. This research is part of a study entitled “Psychoanalytical study on breast cancer” and is included in a Project of the Banco Nacional de DNA, sponsored by the Brazilian Health Ministry.