scholarly journals The Host Genetic Diversity in Malaria Infection

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Vitor R. R. de Mendonça ◽  
Marilda Souza Goncalves ◽  
Manoel Barral-Netto
Keyword(s):  
Genetic Factors ◽  
Inflammatory Responses ◽  
Severe Disease ◽  
Genetic Alterations ◽  
Response To Treatment ◽  
Individual Response ◽  
Genetic Mechanisms ◽  
Host Genetic ◽  
Different Populations ◽  
The Individual

Populations exposed toPlasmodiuminfection develop genetic mechanisms of protection against severe disease. The clinical manifestation of malaria results primarily from the lysis of infected erythrocytes and subsequent immune and inflammatory responses. Herein, we review the genetic alterations associated with erythrocytes or mediators of the immune system, which might influence malaria outcome. Moreover, polymorphisms in genes related to molecules involved in mechanisms of cytoadherence and their influence on malaria pathology are also discussed. The results of some studies have suggested that the combinatorial effects of a set of genetic factors in the erythrocyte-immunology pathway might be relevant to host resistance or susceptibility againstPlasmodiuminfection. However, these results must be interpreted with caution because of the differences observed in the functionality and frequency of polymorphisms within different populations. With the recent advances in molecular biology techniques, more robust studies with reliable data have been reported, and the results of these studies have identified individual genetic factors for consideration in preventing severe disease and the individual response to treatment.

Recent advances in Wilms’ tumor predisposition

2020 ◽  
Vol 29 (R2) ◽  
pp. R138-R149 ◽  
Author(s):  
Jamie L Maciaszek ◽  
Ninad Oak ◽  
Kim E Nichols
Keyword(s):  
Genetic Factors ◽  
Wilms Tumor ◽  
Genetic Diagnosis ◽  
Genetic Alterations ◽  
Epigenetic Alterations ◽  
Familial Cases ◽  
Predisposition Genes ◽  
Host Genetic ◽  
Biological Aspects ◽  
Selective Increase

Abstract Wilms’ tumor (WT), the most common childhood kidney cancer, develops in association with an underlying germline predisposition in up to 15% of cases. Germline alterations affecting the WT1 gene and epigenetic alterations affecting the 11p15 locus are associated with a selective increase in WT risk. Nevertheless, WT also occurs in the context of more pleiotropic cancer predispositions, such as DICER1, Li-Fraumeni and Bloom syndrome, as well as Fanconi anemia. Recent germline genomic investigations have increased our understanding of the host genetic factors that influence WT risk, with sequencing of rare familial cases and large WT cohorts revealing an expanding array of predisposition genes and associated genetic conditions. Here, we describe evidence implicating WT1, the 11p15 locus, and the recently identified genes CTR9, REST and TRIM28 in WT predisposition. We discuss the clinical features, mode of inheritance and biological aspects of tumorigenesis, when known. Despite these described associations, many cases of familial WT remain unexplained. Continued investigations are needed to fully elucidate the landscape of germline genetic alterations in children with WT. Establishing a genetic diagnosis is imperative for WT families so that individuals harboring a predisposing germline variant can undergo surveillance, which should enable the early detection of tumors and use of less intensive treatments, thereby leading to improved overall outcomes.

scholarly journals Current Concepts in Pharmacometabolomics, Biomarker Discovery, and Precision Medicine

Metabolites ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 129 ◽  
Author(s):  
Richard D. Beger ◽  
Michael A Schmidt ◽  
Rima Kaddurah-Daouk
Keyword(s):  
Clinical Trials ◽  
Drug Treatment ◽  
Precision Medicine ◽  
Metabolic Profile ◽  
Biomarker Discovery ◽  
Response To Treatment ◽  
Individual Response ◽  
Patient Response ◽  
Drug Mechanism ◽  
The Individual

Pharmacometabolomics (PMx) studies use information contained in metabolic profiles (or metabolome) to inform about how a subject will respond to drug treatment. Genome, gut microbiome, sex, nutrition, age, stress, health status, and other factors can impact the metabolic profile of an individual. Some of these factors are known to influence the individual response to pharmaceutical compounds. An individual’s metabolic profile has been referred to as his or her “metabotype.” As such, metabolomic profiles obtained prior to, during, or after drug treatment could provide insights about drug mechanism of action and variation of response to treatment. Furthermore, there are several types of PMx studies that are used to discover and inform patterns associated with varied drug responses (i.e., responders vs. non-responders; slow or fast metabolizers). The PMx efforts could simultaneously provide information related to an individual’s pharmacokinetic response during clinical trials and be used to predict patient response to drugs making pharmacometabolomic clinical research valuable for precision medicine. PMx biomarkers can also be discovered and validated during FDA clinical trials. Using biomarkers during medical development is described in US Law under the 21st Century Cures Act. Information on how to submit biomarkers to the FDA and their context of use is defined herein.

scholarly journals Host/genetic factors associated with COVID-19 call for precision medicine

2020 ◽  
Vol 3 (3) ◽  
pp. 228-234
Author(s):  
Alain R Thierry
Keyword(s):  
Precision Medicine ◽  
Genetic Factors ◽  
Inflammatory Responses ◽  
Risk Groups ◽  
Daily Basis ◽  
Severe Illness ◽  
Factors Associated ◽  
Clinical Complications ◽  
Host Genetic ◽  
Host Genetic Factors

Abstract If the current rate of infection are to be better managed, and future waves of infection kept at bay, it is absolutely necessary that the conditions and mechanisms of exposure to Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) be better understood, as well as the downstream severe or lethal clinical complications. While the identification of notable comorbidities has now helped to define broad risk groups, the idiosyncratic responses of individual patients can generate unexpected clinical deterioration that is difficult to predict from initial clinical features. Thus, physicians caring for patients with COVID-19 face clinical dilemmas on a daily basis. The ability to decipher individual predispositions to SARS-CoV-2 infection or severe illness, in light of variations in host immunological and inflammatory responses, in particular as a result of genetic variations, would be of great benefit in infection management. To this end, this work associates the description of COVID-19 clinical complications, comorbidities, sequelae, and environmental and genetic factors. We also give examples of underlying genomic susceptibility to COVID-19, especially with regard to the newly reported link between the disease and the unbalanced formation of neutrophil extracellular traps. As a consequence, we propose that the host/genetic factors associated with COVID-19 call for precision medicine in its treatment. This is to our knowledge the first article describing elements towards precision medicine for patients with COVID-19.

scholarly journals Personalised approaches to pharmacotherapy for schizophrenia

2016 ◽  
Vol 22 (2) ◽  
pp. 78-86 ◽  
Author(s):  
John Lally ◽  
James H. MacCabe
Keyword(s):  
Medical Treatment ◽  
Antipsychotic Medication ◽  
Traditional Approach ◽  
Personalised Medicine ◽  
Individual Characteristics ◽  
Response To Treatment ◽  
Individual Response ◽  
Trial And Error ◽  
Recent Advances ◽  
The Individual

SummaryThe traditional approach to selecting antipsychotic medication involves little more than trial and error. Recent advances in genetics and molecular science offer the hope of a ‘personalised medicine’ approach to antipsychotic development and prescribing in schizophrenia. Personalised medicine is the practice of tailoring medical treatment to the individual characteristics of each patient. In schizophrenia, this will involve the identification of more homogeneous subsets of patients through the application of genetics, epigenetics, proteomics and metabolomics, neuroimaging and other biomarkers, and the use of these findings to stratify patients according to their response to treatment. In this article, we focus on the emerging evidence in pharmacogenetics and biomarkers for assessing individual response and tolerability of antipsychotic medication in schizophrenia.

scholarly journals Impact of Host Genetic Players on Covid-19 Disease Severity: A Review of Current Knowledge and Future Prospect

2021 ◽  
pp. 79-87
Keyword(s):  
Current Knowledge ◽  
Safety Measures ◽  
East Region ◽  
Research Findings ◽  
Host Genetic ◽  
Repurposed Drugs ◽  
Different Populations ◽  
Bangladeshi Population ◽  
The Individual ◽  
Middle East Region

The year 2020 has been more life-changing and eventful than ever due to the COVID-19 which has led us into this worldwide crisis. An interesting revelation has been made that the coronavirus is not entirely new to us as we are being infected by three types of seasonal coronavirus every year in winter resulting in the seasonal cold. However, SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus-2) has pioneered this pandemic in Wuhan, China last year, which has been named COVID-19. Since then, many nations were seen to have responded differently from one another against this virus such as European nations facing more devastation than the Middle East region in this pandemic. The reasons behind these phenomena were assumed to be the different safety measures taken by the nations but in reality, it has been known that the host genetics are responsible for the devastating effects of COVID-19. Many research findings have pointed out that ACE2, TMPRSS2, and HLA genes in the host genomes are responsible for the virus entry and subsequent immune response. Several studies conducted by different nations have found different COVID-19 variations within which three genes seem to provide clues explaining the individual population's differential disease susceptibility and severity of these viral strains. This review paper has summarized the recent research findings on ACE2, TMPRSS2, and HLA gene variations in different populations, and their effect on causing severity of COVID-19 among individuals, which would be helpful to persuade the importance of such patterns in genetic variation within the Bangladeshi population; so that personalized treatment may be formulated or repurposed drugs may be used to lower the profound impact of SARS-CoV-2.

scholarly journals Ten Years of Experience Support Pharmacogenetic Testing to Guide Individualized Drug Therapy

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 160
Author(s):  
María Celsa Peña-Martín ◽  
Belén García-Berrocal ◽  
Almudena Sánchez-Martín ◽  
Elena Marcos-Vadillo ◽  
María Jesús García-Salgado ◽  
...  
Keyword(s):  
Drug Therapy ◽  
Adverse Events ◽  
Precision Medicine ◽  
Drug Efficacy ◽  
Response To Treatment ◽  
Individual Response ◽  
Test Results ◽  
Individualized Drug Therapy ◽  
The Individual ◽  
Multimorbid Patients

Precision medicine utilizing the genetic information of genes involved in the metabolism and disposition of drugs can not only improve drug efficacy but also prevent or minimize adverse events. Polypharmacy is common among multimorbid patients and is associated with increased adverse events. One of the main objectives in health care is safe and efficacious drug therapy, which is directly correlated to the individual response to treatment. Precision medicine can increase drug safety in many scenarios, including polypharmacy. In this report, we share our experience utilizing precision medicine over the past ten years. Based on our experience using pharmacogenetic (PGx)-informed prescribing, we implemented a five-step precision medicine protocol (5SPM) that includes the assessment of the biological–clinical characteristics of the patient, current and past prescription history, and the patient’s PGx test results. To illustrate our approach, we present cases highlighting the clinical relevance of precision medicine with a focus on patients with a complex history and polypharmacy.

scholarly journals Molecular genetic methods in biomedical research. Part III: human gene diagnostics in clinical practice

2021 ◽  
Vol 6 (3) ◽  
pp. 100-109
Author(s):  
A. N. Volkov ◽  
L. V. Nacheva
Keyword(s):  
Low Cost ◽  
Molecular Genetic ◽  
Real Life ◽  
High Sensitivity ◽  
Response To Treatment ◽  
Individual Response ◽  
Technical Simplicity ◽  
The Individual ◽  
Gene Diagnostics ◽  
Pcr Diagnostics

Application of molecular genetic methods in the diagnosis and treatment of human diseases is extremely wide due to a huge amount of hereditary information contained in the human genome. Gene diagnostics allows establishing predisposition to diseases, identification of genetic abnormalities and prediction of pathological outcomes. In addition, gene diagnostics also enables prediction of the individual response to treatment in order to achieve the maximum therapeutic effect. Among all molecular genetic methods, polymerase chain reaction (PCR) diagnostics is a leading approach. Technical simplicity, low cost, high sensitivity and reliability of the method have made PCR diagnostics a routine modality for the risk assessment, diagnostics, and monitoring of the treatment efficiency. Here, we consider the application of PCR diagnostics for the abovementioned tasks and talk about the real-life examples of detecting mutations and chromosomal aberrations which may cause a disease. Further, we discuss the prospects of using a semi-quantitative PCR in medical practice and focus on pharmacogenetics as a key component of a personalised therapy. The lecture is aimed primarily at biomedical students and physicians and represents a continuation of the previous lectures published in Fundamental and Clinical Medicin.

scholarly journals Vaginal microbiome Lactobacillus crispatus is heritable among European American women

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Michelle L. Wright ◽  
Jennifer M. Fettweis ◽  
Lindon J. Eaves ◽  
Judy L. Silberg ◽  
Michael C. Neale ◽  
...  
Keyword(s):  
Genetic Factors ◽  
European Ancestry ◽  
P Value ◽  
European American ◽  
Extrinsic Factors ◽  
American Women ◽  
Lactobacillus Crispatus ◽  
Host Genetic ◽  
Host Genetic Factors ◽  
European American Women

AbstractThe diversity and dominant bacterial taxa in the vagina are reported to be influenced by multiple intrinsic and extrinsic factors, including but not limited to pregnancy, contraceptive use, pathogenic states, socioeconomic status, and ancestry. However, the extent to which host genetic factors influence variation in the vaginal microbiota is unclear. We used a biometrical genetic approach to determine whether host genetic factors contribute to inter-individual differences in taxa from a sample of 332 twins who self-identified as being of African (44 pairs) or European ancestry (122 pairs). Lactobacillus crispatus, a major determinant of vaginal health, was identified as heritable among European American women (narrow-sense heritability = 34.7%, P-value = 0.018). Heritability of L. crispatus is consistent with the reduced prevalence of adverse reproductive disorders, including bacterial vaginosis and preterm birth, among women of European ancestry.

scholarly journals Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eunyoung Emily Lee ◽  
Kyoung-Ho Song ◽  
Woochang Hwang ◽  
Sin Young Ham ◽  
Hyeonju Jeong ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Clustering Analysis ◽  
Validation Cohort ◽  
Inflammatory Responses ◽  
Clinical Course ◽  
Severe Disease ◽  
Outcome Data ◽  
Inflammatory Immune Response ◽  
Cluster 2

AbstractThe objective of the study was to identify distinct patterns in inflammatory immune responses of COVID-19 patients and to investigate their association with clinical course and outcome. Data from hospitalized COVID-19 patients were retrieved from electronic medical record. Supervised k-means clustering of serial C-reactive protein levels (CRP), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC) was used to assign immune responses to one of three groups. Then, relationships between patterns of inflammatory responses and clinical course and outcome of COVID-19 were assessed in a discovery and validation cohort. Unbiased clustering analysis grouped 105 patients of a discovery cohort into three distinct clusters. Cluster 1 (hyper-inflammatory immune response) was characterized by high CRP levels, high ANC, and low ALC, whereas Cluster 3 (hypo-inflammatory immune response) was associated with low CRP levels and normal ANC and ALC. Cluster 2 showed an intermediate pattern. All patients in Cluster 1 required oxygen support whilst 61% patients in Cluster 2 and no patient in Cluster 3 required supplementary oxygen. Two (13.3%) patients in Cluster 1 died, whereas no patient in Clusters 2 and 3 died. The results were confirmed in an independent validation cohort of 116 patients. We identified three different patterns of inflammatory immune response to COVID-19. Hyper-inflammatory immune responses with elevated CRP, neutrophilia, and lymphopenia are associated with a severe disease and a worse outcome. Therefore, targeting the hyper-inflammatory response might improve the clinical outcome of COVID-19.

scholarly journals Histatin-1 Attenuates LPS-Induced Inflammatory Signaling in RAW264.7 Macrophages

2021 ◽  
Vol 22 (15) ◽  
pp. 7856
Author(s):  
Sang Min Lee ◽  
Kyung-No Son ◽  
Dhara Shah ◽  
Marwan Ali ◽  
Arun Balasubramaniam ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cytokine Production ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Mapk Signaling ◽  
Response To Treatment ◽  
No Production ◽  
Inflammatory Signaling ◽  
Raw264.7 Macrophages ◽  
Inflammatory Mediator Production

Macrophages play a critical role in the inflammatory response to environmental triggers, such as lipopolysaccharide (LPS). Inflammatory signaling through macrophages and the innate immune system are increasingly recognized as important contributors to multiple acute and chronic disease processes. Nitric oxide (NO) is a free radical that plays an important role in immune and inflammatory responses as an important intercellular messenger. In addition, NO has an important role in inflammatory responses in mucosal environments such as the ocular surface. Histatin peptides are well-established antimicrobial and wound healing agents. These peptides are important in multiple biological systems, playing roles in responses to the environment and immunomodulation. Given the importance of macrophages in responses to environmental triggers and pathogens, we investigated the effect of histatin-1 (Hst1) on LPS-induced inflammatory responses and the underlying molecular mechanisms in RAW264.7 (RAW) macrophages. LPS-induced inflammatory signaling, NO production and cytokine production in macrophages were tested in response to treatment with Hst1. Hst1 application significantly reduced LPS-induced NO production, inflammatory cytokine production, and inflammatory signaling through the JNK and NF-kB pathways in RAW cells. These results demonstrate that Hst1 can inhibit LPS-induced inflammatory mediator production and MAPK signaling pathways in macrophages.

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