scholarly journals Nonsynonymous variations of ion channel-related genes as risk factors in epilepsy

2021 ◽  
Vol 38 (3) ◽  
pp. 288-293
Author(s):  
Burcu BİTERGE SÜT ◽  
Hayriye SOYTÜRK
Keyword(s):  
Risk Factors ◽  
Ion Channel ◽  
Protein Stability ◽  
Association Studies ◽  
Gene Mutations ◽  
Genetic Association Studies ◽  
Neuronal Membrane ◽  
Functional Explanation ◽  
Missense Mutations ◽  
Functional Annotations

Recurrent seizures are characteristic to epilepsy, which often arise due to increased electrical activity. Ligand-gated ion channels are considered as key factors in epilepsy as they regulate and maintain neuronal membrane potential via regulating ion transportation. Therefore, this study aims to identify ion channel-related single nucleotide variations that are considered as risk factors in epilepsy and determine their potential effects on pathogenicity, protein stability and structure using in silico methods. For this purpose, ion channel-related mutations linked with epilepsy were retrieved from ClinVar. Pathogenicity scores and protein stability were predicted using FATHMM-XF and MUpro, respectively. Structural alterations were determined via HOPE server. We identified 17 epilepsy-related missense mutations, 11 of which were in ion channel-related genes. Nonsynonymous substitutions of p.E177A, p.D219N, p.A322D, p.R577Q, p.E282K, p.V831M and p.R1072C were determined as pathogenic, while all mutations resulted in varying degrees of decrease in overall protein stability. Furthermore, all variants were annotated with risk for disease and introduction of distinct side chains caused differences in size, charge and hydrophobicity, as well as contact with other proteins and ligands. In conclusion, mutations in ion channel-related genes were previously identified in several genetic association studies while their functional annotations were not addressed. The results of this study provide a functional explanation to the pathogenic effects of ion channel-related gene mutations that are considered as risk factors in epilepsy.

scholarly journals Clinical, biochemical and genetic risk factors for 30-day and 5-year mortality in 518 adult patients subjected to cardiopulmonary bypass during cardiac surgery - the INFLACOR study.

2018 ◽  
Vol 65 (2) ◽  
pp. 241-250 ◽  
Author(s):  
Maciej Michał Kowalik ◽  
Romuald Lango ◽  
Piotr Siondalski ◽  
Magdalena Chmara ◽  
Maciej Brzeziński ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Genetic Association ◽  
Biochemical Parameters ◽  
Cox Regression ◽  
Association Studies ◽  
Nyha Class ◽  
Genetic Association Studies ◽  
Chronic Obstructive

There is increasing evidence that genetic variability influence patients’ early morbidity after cardiac surgery performed using cardiopulmonary bypass (CPB). The use of mortality as an outcome measure in cardiac surgical genetic association studies is rare. We publish the 30-day and 5-year survival analyses with focus on pre-, intra-, postoperative variables, biochemical parameters, and genetic variants in the INFLACOR (INFlAmmation in Cardiac OpeRations) cohort.In a series of prospectively recruited 518 adult Polish Caucasians who underwent cardiac surgery in which CPB was used, the clinical data, biochemical parameters, IL-6, soluble ICAM-1, TNFa, soluble E-selectin, and 10 single nucleotide polymorphisms were evaluated for their associations with 30-day and 5-year mortality.The 30-day mortality was associated with: pre-operative prothrombin international normalized ratio, intra-operative blood lactate, postoperative serum creatine phosphokinase, and acute kidney injury requiring renal replacement therapy (AKI-RRT) in logistic regression. Factors that determined the 5-year survival included: pre-operative NYHA class, history of peripheral artery disease and severe chronic obstructive pulmonary disease, intra-operative blood transfusion; and postoperative peripheral hypothermia, myocardial infarction, infection, and AKI-RRT in Cox regression. The serum levels of IL-6 and ICAM-1 measured three hours after operation were associated with 30-day and 5-year mortality, respectively. The ICAM1 rs5498 was associated with 30-day and 5-year survival with borderline significance.Different risk factors determined the early (30-day) and late (5-year) survival after adult cardiac surgery in which cardiopulmonary bypass was used. Future genetic association studies in cardiac surgical patients should adjust for the identified chronic and acute postoperative risk factors.

scholarly journals Ghrelin in Diabetes and Metabolic Syndrome

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Leena Pulkkinen ◽  
Olavi Ukkola ◽  
Marjukka Kolehmainen ◽  
Matti Uusitupa
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Complex Disease ◽  
Association Studies ◽  
Genetic Association Studies ◽  
Public Health Problem ◽  
Basic Research ◽  
Global Public Health

Metabolic syndrome is a cluster of related risk factors for cardiovascular disease, type 2 diabetes and liver disease. Obesity, which has become a global public health problem, is one of the major risk factors for development of metabolic syndrome and type 2 diabetes. Obesity is a complex disease, caused by the interplay between environmental and genetic factors. Ghrelin is one of the circulating peptides, which stimulates appetite and regulates energy balance, and thus is one of the candidate genes for obesity and T2DM. During the last years both basic research and genetic association studies have revealed association between the ghrelin gene and obesity, metabolic syndrome or type 2 diabetes

Genetic Susceptibility to Primary Intracerebral Haemorrhage

2009 ◽  
Vol 4 (1) ◽  
pp. 44 ◽  
Author(s):  
Efthimios Dardiotis ◽  
Efthimios Dardiotis ◽  
Georgia Xiromerisiou ◽  
Konstantinos Paterakis ◽  
Kostas Fountas ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Intracerebral Haemorrhage ◽  
Association Studies ◽  
Cerebral Arteries ◽  
Genetic Association Studies ◽  
Negative Results ◽  
Degenerative Alterations ◽  
Regulation Of Blood Pressure

Primary intracerebral haemorrhage (PICH) originates from the spontaneous rupture of cerebral arteries as a result of chronic degenerative alterations. Although the aetiology of PICH has not been fully elucidated, it may be the result of an interaction between genetic and environmental risk factors. Several genetic association studies have been conducted in patients with PICH with both positive and negative results. Most of them investigated the role of mutations in genes affecting the lipid metabolism, the coagulation processes, the inflammation and the regulation of blood pressure. In this article we briefly discuss the majority of these studies reporting the susceptibility genes that have been implicated in PICH.

Cardiovascular risk factors and Alzheimer's disease: Genetic association studies in a population aged 85+

2000 ◽  
Vol 21 ◽  
pp. 175
Author(s):  
Liisa Myllykangas ◽  
Tuomo Polvikoski ◽  
Raimo Sulkava ◽  
Auli Verkkoniemi ◽  
Pentti Tienari ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Genetic Association ◽  
Association Studies ◽  
Genetic Association Studies

scholarly journals A Comprehensive Review of Molecular Biology and Genetics of Cataract

2021 ◽  
Vol 8 (2) ◽  
pp. 11-20
Author(s):  
Harshal Wasnik ◽  
Rishi Gandhi ◽  
Niraj Patil ◽  
Rajendra Behera ◽  
Anand Golait ◽  
...  
Keyword(s):  
Risk Factors ◽  
Molecular Biology ◽  
Cell Biology ◽  
Association Studies ◽  
Single Gene ◽  
Gene Mutations ◽  
Gene Families ◽  
Genome Wide Association Studies ◽  
Vision 2020 ◽  
Global Initiative

Cataract is one of the oldest diseases. Even in the 21st century, the disease is often neglected and treated as an insignificant threat. Although the facts and figures account for the opposite, it is found that globally cataract holds for more than 50% of blindness. Cataract is also one of the first five immediate focus areas of a global Initiative called 'Vision 2020', which intends to eradicate preventable blindness by 2020. The disease is termed as multifactorial; has various extrinsic environmental and intrinsic cell biology factors determining its progress. Over the years, enormous progress has been made towards cataract including the identification of its risk factors. Yet the current scientific knowledge is far from developing a proven preventive or pharmacological strategy for it. The surgical method has been the only way to cure cataract by far. In this paper, we tried to give a comprehensive bird eye view for the disease; we have (a) reviewed briefly the recent progress in delineating the molecular biology and risk factors of cataract (b) delved into genetics of the cataract and overviewed crucial gene families related to the disease identified through single-gene mutations and Genome-Wide Association Studies (GWAS). 

Statin-induced adverse effects – facts and genes

2013 ◽  
Vol 154 (3) ◽  
pp. 83-92
Author(s):  
Mariann Harangi ◽  
Noémi Zsíros ◽  
Lilla Juhász ◽  
György Paragh
Keyword(s):  
Risk Factors ◽  
Single Nucleotide Polymorphisms ◽  
Adverse Effects ◽  
Adverse Events ◽  
Statin Therapy ◽  
Significant Proportion ◽  
Gene Mutations ◽  
Nucleotide Polymorphisms ◽  
Serious Adverse Events ◽  
Single Nucleotide

Statin therapy is considered to be safe and rarely associated with serious adverse events. However, a significant proportion of patients on statin therapy show some degree of intolerance which can lead to decreased adherence to statin therapy. The authors summarize the symptoms, signs and frequencies of the most common statin-induced adverse effects and their most important risk factors including some single nucleotide polymorphisms and gene mutations. Also, they review the available approaches to detect and manage the statin-intolerant patients. Orv. Hetil., 2013, 154, 83–92.

Review of the Literature Examining the Association of Serum Uric Acid with Osteoporosis and Mechanistic Insights into Its Effect on Bone Metabolism

2019 ◽  
Vol 19 (3) ◽  
pp. 259-273 ◽  
Author(s):  
Neelam Kaushal ◽  
Divya Vohora ◽  
Rajinder K Jalali ◽  
Sujeet Jha
Keyword(s):  
Risk Factors ◽  
Bone Mineral Density ◽  
Uric Acid ◽  
Bone Metabolism ◽  
Serum Uric Acid ◽  
Bone Mineral ◽  
Molecular Mechanisms ◽  
Association Studies ◽  
Mineral Density ◽  
Age Related

Background And Objective:Osteoporosis is a common bone disorder that increases susceptibility to fragility bone fractures. The clinical and public health repercussions of osteoporosis are huge due to the morbidity, mortality, and cost of medical care linked with fragility fractures. Clinical assessment of osteoporotic risk factors can help to identify candidates at an early stage that will benefit from medical intervention and potentially lowering the morbidity and mortality seen with fractures and complications. Given this, research is ongoing to evaluate the association of osteoporosis with some novel or less well-studied risk factors/bio-markers such as uric acid (UA).Discussion:Uric acid’s antioxidant activity has been proposed to be one of the factors responsible for increasing longevity and lowering rates of age-related cancers during primate evolution, the level of which increased markedly due to loss of uricase enzyme activity (mutational silencing). Accumulated evidence shows that oxidative stress is the fundamental mechanism of age-related bone loss and acts via enhancing osteoclastic activity and increasing bone resorption. Antioxidant substances such as ascorbic acid scavenge free radicals are positively related to bone health. Thus, it is hypothesized that uric acid holds bone-protective potential owing to its potent antioxidative property. Several correlation studies have been conducted globally to investigate the relationship between serum uric acid with bone mineral density and osteoporosis. Few pre-clinical studies have tried to investigate the interaction between uric acid and bone mineral density and reported important role played via Runt-related transcription factor 2 (RUNX2)/core-binding factor subunit alpha-1 (CBF-alpha-1), Wingless-related integration site (Wnt)-3a/β-catenin signaling pathway and 11β Hydroxysteroid Dehydrogenase type 1.Conclusion:In this review, the authors provided a comprehensive summary of the literature related to association studies reported in humans as well work done until date to understand the potential cellular and molecular mechanisms that interplay between uric acid and bone metabolism.

scholarly journals Multitrait genetic association analysis identifies 50 new risk loci for gastro-oesophageal reflux, seven new loci for Barrett’s oesophagus and provides insights into clinical heterogeneity in reflux diagnosis

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323906
Author(s):  
Jue-Sheng Ong ◽  
Jiyuan An ◽  
Xikun Han ◽  
Matthew H Law ◽  
Priyanka Nandakumar ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Testing ◽  
Association Studies ◽  
Barrett’S Oesophagus ◽  
Oesophageal Reflux ◽  
Oesophageal Adenocarcinoma ◽  
Specific Gene ◽  
Genome Wide Association Studies ◽  
Disease Heterogeneity ◽  
Barrett's Oesophagus

ObjectiveGastro-oesophageal reflux disease (GERD) has heterogeneous aetiology primarily attributable to its symptom-based definitions. GERD genome-wide association studies (GWASs) have shown strong genetic overlaps with established risk factors such as obesity and depression. We hypothesised that the shared genetic architecture between GERD and these risk factors can be leveraged to (1) identify new GERD and Barrett’s oesophagus (BE) risk loci and (2) explore potentially heterogeneous pathways leading to GERD and oesophageal complications.DesignWe applied multitrait GWAS models combining GERD (78 707 cases; 288 734 controls) and genetically correlated traits including education attainment, depression and body mass index. We also used multitrait analysis to identify BE risk loci. Top hits were replicated in 23andMe (462 753 GERD cases, 24 099 BE cases, 1 484 025 controls). We additionally dissected the GERD loci into obesity-driven and depression-driven subgroups. These subgroups were investigated to determine how they relate to tissue-specific gene expression and to risk of serious oesophageal disease (BE and/or oesophageal adenocarcinoma, EA).ResultsWe identified 88 loci associated with GERD, with 59 replicating in 23andMe after multiple testing corrections. Our BE analysis identified seven novel loci. Additionally we showed that only the obesity-driven GERD loci (but not the depression-driven loci) were associated with genes enriched in oesophageal tissues and successfully predicted BE/EA.ConclusionOur multitrait model identified many novel risk loci for GERD and BE. We present strong evidence for a genetic underpinning of disease heterogeneity in GERD and show that GERD loci associated with depressive symptoms are not strong predictors of BE/EA relative to obesity-driven GERD loci.

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