scholarly journals Genome sequencing reveals the role of rare genomic variants in Chinese patients with symptomatic intracranial atherosclerotic disease

2021 ◽  
pp. svn-2021-001157
Author(s):  
Mengmeng Shi ◽  
Xinyi Leng ◽  
Ying Li ◽  
Zihan Chen ◽  
Ye Cao ◽  
...  
Keyword(s):  
Risk Factors ◽  
Candidate Genes ◽  
Genome Sequencing ◽  
Atherosclerotic Disease ◽  
Chinese Patients ◽  
Genomic Variants ◽  
Stroke Subtypes ◽  
Intracranial Atherosclerotic Disease ◽  
Shared Risk

ObjectivesThe predisposition of intracranial atherosclerotic disease (ICAD) to East Asians over Caucasians infers a genetic basis which, however, remains largely unknown. Higher prevalence of vascular risk factors (VRFs) in Chinese over Caucasian patients who had a stroke, and shared risk factors of ICAD with other stroke subtypes indicate genes related to VRFs and/or other stroke subtypes may also contribute to ICAD.MethodsUnrelated symptomatic patients with ICAD were recruited for genome sequencing (GS, 60-fold). Rare and potentially deleterious single-nucleotide variants (SNVs) and small insertions/deletions (InDels) were detected in genome-wide and correlated to genes related to VRFs and/or other stroke subtypes. Rare aneuploidies, copy number variants (CNVs) and chromosomal structural rearrangements were also investigated. Lastly, candidate genes were used for pathway and gene ontology enrichment analysis.ResultsAmong 92 patients (mean age at stroke onset 61.0±9.3 years), GS identified likely ICAD-associated rare genomic variants in 54.3% (50/92) of patients. Forty-eight patients (52.2%, 48/92) had 59 rare SNVs/InDels reported or predicted to be deleterious in genes related to VRFs and/or other stroke subtypes. None of the 59 rare variants were identified in local subjects without ICAD (n=126). 31 SNVs/InDels were related to conventional VRFs, and 28 were discovered in genes related to other stroke subtypes. Our study also showed that rare CNVs (n=7) and structural rearrangement (a balanced translocation) were potentially related to ICAD in 8.7% (8/92) of patients. Lastly, candidate genes were significantly enriched in pathways related to lipoprotein metabolism and cellular lipid catabolic process.ConclusionsOur GS study suggests a role of rare genomic variants with various variant types contributing to the development of ICAD in Chinese patients.

scholarly journals Personalized medicine in cardio-oncology: the role of induced pluripotent stem cell

2019 ◽  
Vol 115 (5) ◽  
pp. 949-959 ◽  
Author(s):  
Nazish Sayed ◽  
Mohamed Ameen ◽  
Joseph C Wu
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Association Studies ◽  
Induced Pluripotent Stem Cell ◽  
Human Diseases ◽  
Genome Wide Association Studies ◽  
Genomic Variants ◽  
Induced Pluripotent

Abstract Treatment of cancer has evolved in the last decade with the introduction of new therapies. Despite these successes, the lingering cardiotoxic side-effects from chemotherapy remain a major cause of morbidity and mortality in cancer survivors. These effects can develop acutely during treatment, or even years later. Although many risk factors can be identified prior to beginning therapy, unexpected toxicity still occurs, often with lasting consequences. Specifically, cardiotoxicity results in cardiac cell death, eventually leading to cardiomyopathy and heart failure. Certain risk factors may predispose an individual to experiencing adverse cardiovascular effects, and when unexpected cardiotoxicity occurs, it is generally managed with supportive care. Animal models of chemotherapy-induced cardiotoxicity have provided some mechanistic insights, but the precise mechanisms by which these drugs affect the heart remains unknown. Moreover, the genetic rationale as to why some patients are more susceptible to developing cardiotoxicity has yet to be determined. Many genome-wide association studies have identified genomic variants that could be associated with chemotherapy-induced cardiotoxicity, but the lack of validation has made these studies more speculative rather than definitive. With the advent of human induced pluripotent stem cell (iPSC) technology, researchers not only have the opportunity to model human diseases, but also to screen drugs for their efficacy and toxicity using human cell models. Furthermore, it allows us to conduct validation studies to confirm the role of genomic variants in human diseases. In this review, we discuss the role of iPSCs in modelling chemotherapy-induced cardiotoxicity.

scholarly journals Update on Myopia Risk Factors and Microenvironmental Changes

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Valeria Coviltir ◽  
Miruna Burcel ◽  
Alina Popa Cherecheanu ◽  
Catalina Ionescu ◽  
Dana Dascalescu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Environmental Factors ◽  
Signaling Pathways ◽  
Candidate Genes ◽  
Therapeutic Targets ◽  
Current Evidence ◽  
Complex Genetics ◽  
Recent Advances

The focus of this update is to emphasize the recent advances in the pathogenesis and various molecular key approaches associated with myopia in order to reveal new potential therapeutic targets. We review the current evidence for its complex genetics and evaluate the known or candidate genes and loci. In addition, we discuss recent investigations regarding the role of environmental factors. This paper also covers current research aimed at elucidating the signaling pathways involved in the pathogenesis of myopia.

scholarly journals Predictors of Early Infarct Recurrence in Patients With Symptomatic Intracranial Atherosclerotic Disease

Stroke ◽  
2021 ◽  
Author(s):  
Shyam Prabhakaran ◽  
David S. Liebeskind ◽  
George Cotsonis ◽  
Azhar Nizam ◽  
Edward Feldmann ◽  
...  
Keyword(s):  
Risk Factors ◽  
Odds Ratio ◽  
Diffusion Weighted Imaging ◽  
Adjusted Odds Ratio ◽  
Recurrent Stroke ◽  
Brain Mri ◽  
Atherosclerotic Disease ◽  
Intracranial Atherosclerotic Disease ◽  
Diffusion Weighted ◽  
Artery Embolism

Background and Purpose: While prior studies identified risk factors for recurrent stroke in patients with symptomatic intracranial atherosclerotic disease, few have assessed risk factors for early infarct recurrence. Methods: We performed a post hoc analysis of the MYRIAD study (Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease) of intracranial atherosclerotic disease patients with recent (<21 days) stroke/transient ischemic attack, 50% to 99% stenosis and who underwent 6- to 8-week magnetic resonance imaging (MRI) per protocol. Infarct recurrence was defined as new infarcts in the territory of the symptomatic artery on brain MRI at 6 to 8 weeks compared to index brain MRI. Qualifying events and clinical and imaging outcomes were centrally ascertained by 2 independent reviewers. We assessed the association between baseline clinical and imaging variables and recurrent infarct in bivariate models and multivariable logistic regression to identify independent predictors of infarct recurrence. Results: Of 105 enrolled patients in MYRIAD, 89 (84.8%) were included in this analysis (mean age, 64±12 years, 54 [60.7%] were male, and 53 [59.6%] were White). The median time from qualifying event to MRI was 51+16 days, on which 22 (24.7%) patients had new or recurrent infarcts. Younger age (57.7 versus 66.0 years; P <0.01), diabetes (32.6% versus 14.6%, P =0.05), index stroke (31.3% versus 4.6%, P =0.01), anterior circulation location of stenosis (29.7% versus 12.0%, P =0.08), number of diffusion-weighted imaging lesions (>1: 40.0%, 1: 26.9% versus 0: 4.4%, P <0.01), and borderzone infarct pattern (63.6% versus 25.0%, P =0.01) on baseline MRI were associated with new or recurrent infarcts. Age (adjusted odds ratio, 0.93 [95% CI, 0.89–0.98], P <0.01) and number of diffusion-weighted imaging lesions (adjusted odds ratio, 3.24 [95% CI, 1.36–7.71], P <0.01) were independently associated with recurrent infarct adjusting for hypertension, diabetes, and stenosis location (anterior versus posterior circulation). Conclusions: An index multi-infarct pattern is associated with early recurrent infarcts, a finding that might be explained by plaque instability and artery-to-artery embolism. Further investigation of plaque vulnerability in intracranial atherosclerotic disease is needed. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02121028.

Chronic Inflammatory Diseases and Atherosclerotic Cardiovascular Disease: Innocent Bystanders or Partners in Crime?

2018 ◽  
Vol 24 (3) ◽  
pp. 281-290 ◽  
Author(s):  
Peter Riis Hansen
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Inflammatory Diseases ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Chronic Inflammatory Diseases ◽  
Increased Risk ◽  
Shared Risk

Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future prospects in this area of research. Awareness of the role of inflammation in CVD in patients with chronic inflammatory diseases and the potential for anti-inflammatory therapy, e.g., with tumor necrosis factor-α inhibitors, to also reduce atherosclerotic CVD has evolved into guideline- based recommendations. These include regular CVD risk assessment, aggressive treatment of traditional CVD risk factors, and recognition of reduced CVD as an added benefit of strict inflammatory disease control. At present, chronic inflammatory diseases would appear to qualify as partners in crime and not merely innocent bystanders to CVD. However, definite incremental contributions of inflammation versus effects of the complex interplay with other CVD risk factors may never be fully elucidated and for the foreseeable future, inflammation is posed to maintain its current position as both a marker and a maker of CVD, with clinical utility both for identification of patient at risk of CVD and as target for therapy to reduce CVD.

scholarly journals Diabetes and cancer II: role of diabetes medications and influence of shared risk factors

2012 ◽  
Vol 23 (7) ◽  
pp. 991-1008 ◽  
Author(s):  
Adedayo A. Onitilo ◽  
Jessica M. Engel ◽  
Ingrid Glurich ◽  
Rachel V. Stankowski ◽  
Gail M. Williams ◽  
...  
Keyword(s):  
Risk Factors ◽  
Shared Risk

scholarly journals Preeclampsia and ESRD: The Role of Shared Risk Factors

2017 ◽  
Vol 69 (4) ◽  
pp. 498-505 ◽  
Author(s):  
Andrea G. Kattah ◽  
Dawn C. Scantlebury ◽  
Sanket Agarwal ◽  
Michelle M. Mielke ◽  
Walter A. Rocca ◽  
...  
Keyword(s):  
Risk Factors ◽  
Shared Risk

scholarly journals The Evolving Paradigm in the Management of Intracranial Atherosclerotic Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-5
Author(s):  
Ali K. Ozturk ◽  
Ketan R. Bulsara
Keyword(s):  
English Literature ◽  
Treatment Options ◽  
Atherosclerotic Disease ◽  
Endovascular Techniques ◽  
Intracranial Atherosclerotic Disease ◽  
History Of ◽  
Recurrent Strokes ◽  
Rigorous Treatment ◽  
Significant Health

Intracranial atherosclerotic disease (ICAD) is a major cause of ischemic stroke worldwide and represents a significant health problem. The pathogenesis and natural history of ICAD are poorly understood, and rigorous treatment paradigms do not exist as they do for extracranial atherosclerosis. Currently, the best treatment for ICAD remains aspirin therapy, but many patients who are placed on aspirin continue to experience recurrent strokes. As microsurgical and endovascular techniques continue to evolve, the role of extracranial to intracranial bypass operations and stenting are increasingly being reconsidered. We performed a PubMed review of the English literature with a particular focus on treatment options for ICAD and present evidence-based data for the role of surgery and stenting in ICAD against medical therapy alone.

Abstract 68: Impaired Perfusion in Intracranial Atherosclerotic Disease Predicts Cognitive Outcomes

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
David S Liebeskind ◽  
Jose G Romano ◽  
George A Cotsonis ◽  
Shadi Yaghi ◽  
Tristan Honda ◽  
...  
Keyword(s):  
Collateral Circulation ◽  
Recurrent Stroke ◽  
Cognitive Outcomes ◽  
Cognitive Testing ◽  
Atherosclerotic Disease ◽  
Collateral Flow ◽  
Cognitive Changes ◽  
Intracranial Atherosclerotic Disease ◽  
Antegrade Flow

Background: Poor collateral circulation and hypoperfusion may lead to recurrent stroke in intracranial atherosclerotic disease (ICAD). The role of perfusion in silent strokes and potentially insidious cognitive impairment in ICAD is unknown. We used evidence of impaired perfusion at angiography in SAMMPRIS to predict subsequent cognitive changes. Methods: Angiography at enrollment in the SAMMPRIS trial was independently evaluated, blind to clinical data and cognitive testing. Antegrade flow in the symptomatic arterial territory and corresponding collateral flow were scored. Impaired perfusion was defined by poor antegrade and poor collateral flow. Serial testing with the Montreal Cognitive Assessment (MoCA) was done in subjects without aphasia or neglect at baseline, 4 mo, 12 mo and closeout, or until subjects had a clinical stroke endpoint. Results: 207 subjects (median age 61, range 33-81 years; 37% women) had baseline MoCA scores with angiography data on territorial perfusion. Baseline MoCA scores (mean 24.2±4.1) were similar between categories of antegrade flow and collateral circulation. Impaired perfusion was noted in 33/207 (16%). Serial MoCA revealed that changes in cognition over time were different at 4 mo, 12 mo and closeout based on the presence of impaired perfusion at baseline (p<0.001). After more modest (mean MoCA change = 0.5 increase from baseline, p=0.80) early improved cognitive function at 4 mo, those with impaired perfusion had cognitive decline at 12 mo (mean MoCA change, p<0.01) unlike the continued improvement in other subjects. Cognitive changes in those with impaired perfusion were associated with a higher frequency of subsequent stroke in the territory. Conclusions: Impaired perfusion in the symptomatic arterial territory of ICAD predicts cognitive outcomes that may precede recurrent ischemia. Future studies may define the role of noninvasive perfusion imaging in ICAD to predict cognitive trajectories and recurrent stroke.

Abstract WP207: Serum Urate As A Potential Risk Factor For Intracranial Atherosclerotic Disease

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Xin Wan ◽  
Chengbo Dai ◽  
Xiong Zhang ◽  
Shuo Wang ◽  
Yumin Cao ◽  
...  
Keyword(s):  
Risk Factors ◽  
Elevated Serum ◽  
Serum Urate ◽  
Atherosclerotic Disease ◽  
Control Group ◽  
Large Artery ◽  
Intracranial Atherosclerotic Disease ◽  
Serum Urate Level ◽  
Independent Risk Factors ◽  
The Relationship

Introduction While serum urate is associated with cardiovascular disease, the relationship between serum urate and cerebrovascular atherosclerotic diseases remains controversial. Intracranial atherosclerotic disease (ICAD) is more prone to affect Asian population and the most common cause of ischemic stroke in China. There are few studies observed the associations between serum urate and ICAD. Hypothesis We assessed the hypothesis that elevated serum urate level is associated with intracranial atherosclerotic disease and serum urate is a potential risk factor for intracranial atherosclerotic disease. Methods Clinical data of 411 patients undergoing cerebral angiography were analyzed, and they were separated into groups according to the findings of cerebral angiography: Extracranial cerebral artery atherosclerosis (ECAA) group included 115 patients had at least one of extracranial carotid or vertebral arteries was stenosised beyond 50%; intracranial atherosclerotic disease(ICAD) group included 173 patients had at least one of intracranial large artery was stenosised beyond 50%; control group included 123 patients had none cerebral large artery stenosis. The relationship between serum urate level and ICAD was explored. Results The mean serum urate level of ICA group(345.50±95.83μmol/L) and ECCA group(337.71±98.72μmol/L) are significantly higher than control group(298.21±83.85μmol/L, P <0.01), and the ICAD group had a markedly higher rate of patients that had abnormal serum urate level than control group (the proportion of patients that serum urate level above 420μmol/L in ICAD and control group is 23.4% and 11% respectively, P <0.05). The proportion of ICAD patients increased significantly with the raise of serum urate level (we divided all the patients into 4 groups according to the quartiles of serum urate level, the proportion of ICAD patients of each group is 31.9%, 36.2%, 47.1% and 52.9% respectively, χ 2 = 7.898 , P =0.048). Logistic regression analysis shows that serum urate level is one of the independent risk factors of ICAD (OR=1.0007, 95%CI:1.003-1.011, P <0.05). Conclusion The elevated serum urate level is correlate with ICAD and is a underlying independent risk factors of ICAD.

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