scholarly journals Genetic variants in Barrett's esophagus and esophageal adenocarcinoma: a literature review

2019 ◽  
Vol 32 (8) ◽  
Author(s):  
Zachary M Callahan ◽  
Zhuqing Shi ◽  
Bailey Su ◽  
Jianfeng Xu ◽  
Michael Ujiki
Keyword(s):  
Barrett’S Esophagus ◽  
Esophageal Adenocarcinoma ◽  
Barrett's Esophagus ◽  
Association Studies ◽  
Genetic Alterations ◽  
Genome Wide Association Studies ◽  
Endoscopic Screening ◽  
Genome Wide ◽  
Current Screening

SUMMARY Surveillance of Barrett's esophagus (BE) is a clinical challenge; metaplasia of the distal esophagus increases a patient's risk of esophageal adenocarcinoma (EAC) significantly but the actual percentage of patients who progress is low. The current screening recommendations require frequent endoscopy and biopsy, which has inherent risk, high cost, and operator variation. Identifying BE patients genetically who are at high risk of progressing could deemphasize the role of endoscopic screening and create an opportunity for early therapeutic intervention. Genetic alterations in germline DNA have been identified in other disease processes and allow for early intervention or surveillance well before disease develops. The genetic component of BE remains mostly unknown and only a few genome-wide association studies exist on this topic. This review summarizes the current literature available that examines genetic alterations in BE and EAC with a particular emphasis on clinical implications.

scholarly journals Implications of Recent Revelations from Basic and Clinical Studies of Barrett’s Esophagus for Screening and Surveillance Strategies

2021 ◽  
Vol 1 (1) ◽  
pp. 86-92
Author(s):  
Stuart Jon Spechler ◽  
Rhonda F. Souza
Keyword(s):  
High Risk ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Prevention Strategies ◽  
Endoscopic Screening ◽  
Screening Practices ◽  
The Past ◽  
Screening And Surveillance ◽  
Gerd Symptoms ◽  
Current Screening

During the past several decades, while the incidence of esophageal adenocarcinoma (EAC) has risen dramatically, our primary EAC-prevention strategies have been endoscopic screening of individuals with GERD symptoms for Barrett’s esophagus (BE), and endoscopic surveillance for those found to have BE. Unfortunately, current screening practices have failed to identify most patients who develop EAC, and the efficacy of surveillance remains highly questionable. We review potential reasons for failure of these practices including recent evidence that most EACs develop through a rapid genomic doubling pathway, and recent data suggesting that many EACs develop from segments of esophageal intestinal metaplasia too short to be recognized as BE. We highlight need for a biomarker to identify BE patients at high risk for neoplasia (who would benefit from early therapeutic intervention), and BE patients at low risk (who would not benefit from surveillance). Promising recent efforts to identify such a biomarker are reviewed herein.

scholarly journals Genetic Determinants of Paget’s Disease of Bone

2021 ◽  
Author(s):  
Navnit S. Makaram ◽  
Stuart H. Ralston
Keyword(s):  
Genetic Factors ◽  
Association Studies ◽  
Paget’S Disease ◽  
Paget's Disease ◽  
Paget’S Disease Of Bone ◽  
Genome Wide Association Studies ◽  
Paget's Disease Of Bone ◽  
Genome Wide ◽  
Family Based

Abstract Purpose of Review To provide an overview of the role of genes and loci that predispose to Paget’s disease of bone and related disorders. Recent Findings Studies over the past ten years have seen major advances in knowledge on the role of genetic factors in Paget’s disease of bone (PDB). Genome wide association studies have identified six loci that predispose to the disease whereas family based studies have identified a further eight genes that cause PDB. This brings the total number of genes and loci implicated in PDB to fourteen. Emerging evidence has shown that a number of these genes also predispose to multisystem proteinopathy syndromes where PDB is accompanied by neurodegeneration and myopathy due to the accumulation of abnormal protein aggregates, emphasising the importance of defects in autophagy in the pathogenesis of PDB. Summary Genetic factors play a key role in the pathogenesis of PDB and the studies in this area have identified several genes previously not suspected to play a role in bone metabolism. Genetic testing coupled to targeted therapeutic intervention is being explored as a way of halting disease progression and improving outcome before irreversible skeletal damage has occurred.

Stroke Genetics: Turning Discoveries into Clinical Applications

Stroke ◽  
2021 ◽  
Author(s):  
Martin Dichgans ◽  
Nathalie Beaufort ◽  
Stephanie Debette ◽  
Christopher D. Anderson
Keyword(s):  
Mendelian Randomization ◽  
Association Studies ◽  
Clinical Applications ◽  
Risk Scores ◽  
Genome Wide Association Studies ◽  
Neuroprotective Agents ◽  
Experimental Systems ◽  
Genome Wide ◽  
Rapid Pace

The field of medical and population genetics in stroke is moving at a rapid pace and has led to unanticipated opportunities for discovery and clinical applications. Genome-wide association studies have highlighted the role of specific pathways relevant to etiologically defined subtypes of stroke and to stroke as a whole. They have further offered starting points for the exploration of novel pathways and pharmacological strategies in experimental systems. Mendelian randomization studies continue to provide insights in the causal relationships between exposures and outcomes and have become a useful tool for predicting the efficacy and side effects of drugs. Additional applications that have emerged from recent discoveries include risk prediction based on polygenic risk scores and pharmacogenomics. Among the topics currently moving into focus is the genetics of stroke outcome. While still at its infancy, this field is expected to boost the development of neuroprotective agents. We provide a brief overview on recent progress in these areas.

scholarly journals Current knowledge in hypertension genetics: mosaic theory, candidate genes and genome-wide association studies

2020 ◽  
Vol 26 (5) ◽  
pp. 490-500
Author(s):  
A. O. Konradi
Keyword(s):  
Candidate Genes ◽  
High Performance ◽  
New Technologies ◽  
Current Knowledge ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Modern Approach ◽  
Genome Wide

The article reviews monogenic forms of hypertension, data on the role of heredity of essential hypertension and candidate genes, as well as genome-wide association studies. Modern approach for the role of genetics is driven by implementation of new technologies and their productivity. High performance speed of new technologies like genome-wide association studies provide data for better knowledge of genetic markers of hypertension. The major goal nowadays for research is to reveal molecular pathways of blood pressure regulation, which can help to move from populational to individual level of understanding of pathogenesis and treatment targets.

Vascular contributions to cognitive impairment and dementia: the emerging role of 20-HETE

2021 ◽  
Vol 135 (15) ◽  
pp. 1929-1944
Author(s):  
Ezekiel Gonzalez-Fernandez ◽  
Yedan Liu ◽  
Alexander P. Auchus ◽  
Fan Fan ◽  
Richard J. Roman
Keyword(s):  
Cognitive Impairment ◽  
Association Studies ◽  
Amyloid Β ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Cerebrovascular Risk ◽  
Potent Vasoconstrictor ◽  
Multiple Drugs ◽  
Epidemiology Studies

Abstract The accumulation of extracellular amyloid-β (Aβ) and intracellular hyperphosphorylated τ proteins in the brain are the hallmarks of Alzheimer’s disease (AD). Much of the research into the pathogenesis of AD has focused on the amyloid or τ hypothesis. These hypotheses propose that Aβ or τ aggregation is the inciting event in AD that leads to downstream neurodegeneration, inflammation, brain atrophy and cognitive impairment. Multiple drugs have been developed and are effective in preventing the accumulation and/or clearing of Aβ or τ proteins. However, clinical trials examining these therapeutic agents have failed to show efficacy in preventing or slowing the progression of the disease. Thus, there is a need for fresh perspectives and the evaluation of alternative therapeutic targets in this field. Epidemiology studies have revealed significant overlap between cardiovascular and cerebrovascular risk factors such as hypertension, diabetes, atherosclerosis and stroke to the development of cognitive impairment. This strong correlation has given birth to a renewed focus on vascular contributions to AD and related dementias. However, few genes and mechanisms have been identified. 20-Hydroxyeicosatetraenoic acid (20-HETE) is a potent vasoconstrictor that plays a complex role in hypertension, autoregulation of cerebral blood flow and blood–brain barrier (BBB) integrity. Multiple human genome-wide association studies have linked mutations in the cytochrome P450 (CYP) 4A (CYP4A) genes that produce 20-HETE to hypertension and stroke. Most recently, genetic variants in the enzymes that produce 20-HETE have also been linked to AD in human population studies. This review examines the emerging role of 20-HETE in AD and related dementias.

scholarly journals Heritability jointly explained by host genotype and microbiome: will improve traits prediction?

2020 ◽  
Author(s):  
Denis Awany ◽  
Emile R Chimusa
Keyword(s):  
Genetic Variants ◽  
Association Studies ◽  
Heritability Estimate ◽  
Substantial Part ◽  
Phenotypic Variance ◽  
Genome Wide Association Studies ◽  
Host Genotype ◽  
Genome Wide ◽  
Heritability Estimation

Abstract As we observe the $70$th anniversary of the publication by Robertson that formalized the notion of ‘heritability’, geneticists remain puzzled by the problem of missing/hidden heritability, where heritability estimates from genome-wide association studies (GWASs) fall short of that from twin-based studies. Many possible explanations have been offered for this discrepancy, including existence of genetic variants poorly captured by existing arrays, dominance, epistasis and unaccounted-for environmental factors; albeit these remain controversial. We believe a substantial part of this problem could be solved or better understood by incorporating the host’s microbiota information in the GWAS model for heritability estimation and may also increase human traits prediction for clinical utility. This is because, despite empirical observations such as (i) the intimate role of the microbiome in many complex human phenotypes, (ii) the overlap between genetic variants associated with both microbiome attributes and complex diseases and (iii) the existence of heritable bacterial taxa, current GWAS models for heritability estimate do not take into account the contributory role of the microbiome. Furthermore, heritability estimate from twin-based studies does not discern microbiome component of the observed total phenotypic variance. Here, we summarize the concept of heritability in GWAS and microbiome-wide association studies, focusing on its estimation, from a statistical genetics perspective. We then discuss a possible statistical method to incorporate the microbiome in the estimation of heritability in host GWAS.

scholarly journals Inositol 1,4,5-Trisphosphate Receptors in Human Disease: A Comprehensive Update

2020 ◽  
Vol 9 (4) ◽  
pp. 1096
Author(s):  
Jessica Gambardella ◽  
Angela Lombardi ◽  
Marco Bruno Morelli ◽  
John Ferrara ◽  
Gaetano Santulli
Keyword(s):  
Human Disease ◽  
Calcium Release ◽  
Current Knowledge ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Loss Of Function ◽  
Genome Wide ◽  
Inositol 1,4,5 Trisphosphate ◽  
Human Disorders

Inositol 1,4,5-trisphosphate receptors (ITPRs) are intracellular calcium release channels located on the endoplasmic reticulum of virtually every cell. Herein, we are reporting an updated systematic summary of the current knowledge on the functional role of ITPRs in human disorders. Specifically, we are describing the involvement of its loss-of-function and gain-of-function mutations in the pathogenesis of neurological, immunological, cardiovascular, and neoplastic human disease. Recent results from genome-wide association studies are also discussed.

Role of EUS in patients with suspected Barrett’s esophagus with high-grade dysplasia or early esophageal adenocarcinoma: impact on endoscopic therapy

2017 ◽  
Vol 86 (2) ◽  
pp. 292-298 ◽  
Author(s):  
Michael J. Bartel ◽  
Timothy M. Wallace ◽  
Rene D. Gomez-Esquivel ◽  
Massimo Raimondo ◽  
Herbert C. Wolfsen ◽  
...  
Keyword(s):  
Barrett’S Esophagus ◽  
Esophageal Adenocarcinoma ◽  
Barrett's Esophagus ◽  
Endoscopic Therapy ◽  
High Grade Dysplasia ◽  
High Grade
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