Advances in the Genetic Basis of Ischemic Stroke

Advances in the Genetic Basis of Ischemic StrokeAs one of the leading causes of death within both the developed and developing world, stroke is a world-wide problem. About 80% of strokes are ischemic. It is caused by multiple genetic factors, environmental factors, and interactions among these factors. There is a long list of candidate genes that have been studied for a possible association with ischemic stroke. Among the most widely investigated genes are those involved in haemostasis, inflammation, nitric oxide production, homocysteine and lipid metabolism, renin-angiotensin-aldosterone system. Combined link-age/association studies have demonstrated that genes encoding PDE4D and ALOX5AP confer risk for stroke. We review the studies of these genes which may have potential application on the early diagnosis, prevention and treatment ischemic stroke patients.

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Molecular Genetics of Migraine Headaches: A Review

Cephalalgia ◽

10.1046/j.1468-2982.2000.00003.x ◽

2000 ◽

Vol 20 (1) ◽

pp. 3-14 ◽

Cited By ~ 69

Author(s):

P Montagna

Keyword(s):

Serotonin Receptors ◽

Genetic Linkage ◽

World Wide ◽

Genetic Basis ◽

Association Studies ◽

Familial Hemiplegic Migraine ◽

Success Story ◽

Hemiplegic Migraine ◽

Migraine Headaches ◽

Prothrombotic Risk Factors

Following the recent discovery of neural calcium channel mutations in familial hemiplegic migraine, genetic linkage and association studies have been performed world-wide in an effort to unveil the genetic basis of the more common types of migraine too. Mutations in neural calcium channels, rnitochondrial DNA, serotonin receptors and transporter, dopamine receptors and genetic prothrombotic risk factors have been especially investigated and are discussed here. No unambiguous conclusions have, however, been reached. FHM remains an isolated success story in the quest for the genetic basis of migraine.

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Study on Stroke among Hypertensive Patients in a Teaching Hospital

TAJ Journal of Teachers Association ◽

10.3329/taj.v27i2.37636 ◽

2018 ◽

Vol 27 (2) ◽

pp. 30-32

Author(s):

T Islam ◽

MN Huda ◽

S Hossain ◽

MN Islam ◽

E Huq ◽

...

Keyword(s):

Risk Factor ◽

Ischemic Stroke ◽

Antihypertensive Treatment ◽

Causes Of Death ◽

Hemorrhagic Stroke ◽

Stroke Patients ◽

College Hospital ◽

Hypertensive Patients ◽

Medical College ◽

The World

Stroke is one of the commonest causes of death and disability in the world. Hypertension is the greatest treatable risk factor for both ischernic and hemorrhagic stroke. This study was carried out in Rajshahi Medical College Hospital to observe the incidence of stroke among hypertensive patients and to compare the occurrence of stroke among patients who were taking anti-hypertensive drugs regularly and those who were taking irregularly. Hundred stroke patients with hypertension were selected randomly. Ischemic stroke 66% and hemorrhagic stroke 34% was observed. Majority (64%) of hypertensive patient was treated irregularly and only 36% patients were treated regularly with drugs. Incidence of ischemic (66.6%) and hemorrhagic (58.8%) stroke was increased in irregularly antihypertensive treatment patients.TAJ 2014; 27(2): 30-32

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Abstract 3206: Obesity Paradox in Acute Ischemic Stroke: Analysis of 34,132 Patients from Korean Stroke Registry

Stroke ◽

10.1161/str.43.suppl_1.a3206 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Beom Joon Kim ◽

Seung-Hoon Lee ◽

Keun-Hwa Jung ◽

Kyung-Ho Yu ◽

Byung-Chul Lee ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Causes Of Death ◽

Obesity Paradox ◽

Inverse Association ◽

Age Group ◽

Stroke Patients ◽

Stroke Registry ◽

Risk Of Mortality ◽

Obesity Status

Background. Paradoxical longevity in obese patients with established disease has been reported in various conditions. However, detailed investigations involving acute ischemic stroke patients are scarce. We aimed to detect obesity paradox in acute ischemic stroke patients with stratified analyses based on age and causes of mortality. Methods. Korean Stroke Registry (KSR) is a nationwide, multicenter and prospective registry of acute stroke. During 7.5 years, 34 132 acute ischemic stroke patients were collected through 30 participating centers. The mortality information was ascertained through a governmental statistical office, as current of December 2009. Multiple imputation by IVEware was used to estimate missing data on the basis of observed information and to account for potential variance due to uncertainty of missingness. Results. Among a total of 34,132 acute ischemic stroke patients analyzed in this study, 1,348 patients (4.7%) were classified as underweighted (BMI <18.5), 10,888 (37.7%) as normal weight (18.5 - 22.9), 7,666 (26.5%) as overweight (23 - 24.9), 8,056 (27.9%) as obesity I (25.0 - 29.9), and 924 (3.2%) as obesity II (≥30; BMI missing in 5,250 patients), at the time of admission. During mean follow-up of 32.6 ± 23.1 months, 9,073 patients (26.6%) were deceased up to June 2009. Mortality rates of the included patients at various time-points were as followed; 4.1% (1,410 subjects) at 1-month, 7.0% (2,394) at 3-month, and 13.0% (4,373) at 1-year after stroke. Compared with body mass index (BMI) value of 20 - 23, stroke survivors with lower BMI values had increased risk of mortality (HR 1.36, 95% CI 1.25 - 1.48 for BMI ≤18.5; HR 1.14, 95% CI 1.03 - 1.26 for BMI 18.5 - 20). Likewise, obese stroke patients had decreased risk of mortality (HR 0.83, 95% CI 0.74 - 0.92 for BMI 27.5 - 30; HR 0.77, 95% CI 0.63 - 0.93 for BMI 30 - 32.5; see Figure ). Inverse association between obesity status and mortality was not evident until 90 days after stroke, but became significant 1 year after onset of stroke. The association between obesity status and mortality was stronger in young-age group than in old-age group, but significance was maintained through all age-strata. The obesity paradox remained significant regardless of mortality causes, such as cancer death, vascular death and other causes of death. Conclusion. From our study, an inverse association between obesity status and long-term mortality in stroke survivors was documented, and such association was evident regardless of age or causes of death.

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Ischemic Stroke with Troponin Elevation: Patient Characteristics, Resource Utilization, and In-Hospital Outcomes

Cerebrovascular Diseases ◽

10.1159/000445526 ◽

2016 ◽

Vol 42 (3-4) ◽

pp. 213-223 ◽

Cited By ~ 5

Author(s):

Krishi Peddada ◽

Salvador Cruz-Flores ◽

Larry B. Goldstein ◽

Eliahu Feen ◽

Kevin F. Kennedy ◽

...

Keyword(s):

Ischemic Stroke ◽

Hospital Mortality ◽

Clinical Characteristics ◽

Causes Of Death ◽

Mortality Rates ◽

Hospital Death ◽

Stroke Patients ◽

Troponin Elevation ◽

Changes Over Time ◽

Over Time

Background: Among patients hospitalized for acute ischemic stroke, abnormal serum troponins are associated with higher risk of short-term mortality. However, most findings have been reported from European hospitals. Whether troponin elevation after stroke is independently associated with death among a more heterogeneous US population remains unclear. Furthermore, only a few studies have evaluated the association between the magnitude of troponin elevation and subsequent mortality, patterns of dynamic troponin changes over time, or whether troponin elevation is related to specific causes of death. Methods: Using data collected in the American Heart Association's ‘Get With The Guidelines' stroke registry between 2008 and 2012 at a tertiary care US hospital, we used logistic regression to evaluate the independent relationship between troponin elevation and mortality after adjusting for demographic and clinical characteristics. We then assessed whether the magnitude of troponin elevation was related to in-hospital mortality by calculating mortality rates according to tertiles of peak troponin levels. Dynamic troponin changes over time were evaluated as well. To better understand whether troponin elevation identified patients most likely to die due to a specific cause of death, investigators blinded from troponin values reviewed all in-hospital deaths, and the association between troponin elevation and mortality was evaluated among patients with cardiac, neurologic, or other causes of death. Results: Of 1,145 ischemic stroke patients, 199 (17%) had elevated troponin levels. Troponin-positive patients had more cardiovascular risk factors, more intensive medical therapy, and greater use of cardiac procedures. These individuals had higher in-hospital mortality rates than troponin-negative patients (27 vs. 8%, p < 0.001), and this association persisted after adjustment for 13 clinical and management variables (OR 4.28, 95% CI 2.40-7.63). Any troponin elevation was associated with higher mortality, even at very low peak troponin levels (mortality rates 24-29% across tertiles of troponin). Patients with persistently rising troponin levels had fewer anticoagulant and antiatherosclerotic therapies, with markedly worse outcomes. Furthermore, troponin-positive patients had higher rates of all categories of death: neurologic (17 vs. 7%), cardiac (5 vs. <1%), and other causes of death (5 vs. <1%; p < 0.001 for all comparisons). Conclusions: Ischemic stroke patients with abnormal troponin levels are at higher risk of in-hospital death, even after accounting for demographic and clinical characteristics, and any degree of troponin elevation identifies this higher level of risk. Troponins that continue to rise during the hospitalization identify stroke patients at markedly higher risk of mortality, and both neurologic and non-neurologically mediated mortality rates are higher when troponin is elevated.

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Identification and Functional Studies of MYO1H for Mandibular Prognathism

Journal of Dental Research ◽

10.1177/0022034518784936 ◽

2018 ◽

Vol 97 (13) ◽

pp. 1501-1509 ◽

Cited By ~ 6

Author(s):

R. Sun ◽

Y. Wang ◽

M. Jin ◽

L. Chen ◽

Y. Cao ◽

...

Keyword(s):

Genetic Basis ◽

Genetic Factors ◽

Association Studies ◽

Cartilage Defects ◽

Orthologous Genes ◽

Mandibular Prognathism ◽

Functional Studies ◽

Causal Genes ◽

Embryologic Development ◽

Functional Analyses

Mandibular prognathism (MP) is regarded as a craniofacial deformity resulting from the combined effects of environmental and genetic factors, while the genetically predetermined component is considered to play an important role to develop MP. Although linkage and association studies for MP have identified multiple strongly associated regions and genes, the causal genes and variants responsible for the deformity remain largely undetermined. To address this, we performed targeted sequencing of 396 genes selected from previous studies as well as genes and pathways related with craniofacial development as primary candidates in 199 MP cases and 197 controls and carried out a series of statistical and functional analyses. A nonsynonymous common variant of MYO1H rs3825393, C>T, p.Pro1001Leu, was identified to be significantly associated with MP. During zebrafish embryologic development, expression of MYO1H orthologous genes were detected at mandibular jaw. Furthermore, jaw cartilage defects were observed in zebrafish knockdown models. Collectively, these data demonstrate that MYO1H is required for proper jaw growth and contributes to MP pathogenesis, expanding our knowledge of the genetic basis of MP.

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Stratifying depression by neuroticism: revisiting a diagnostic tradition using GWAS data

10.1101/547828 ◽

2019 ◽

Author(s):

Mark J. Adams ◽

David M. Howard ◽

Michelle Luciano ◽

Toni-Kim Clarke ◽

Gail Davies ◽

...

Keyword(s):

Genetic Basis ◽

Genetic Variance ◽

Genetic Factors ◽

Association Studies ◽

Genetic Correlations ◽

Genome Wide Association Studies ◽

Summary Statistics ◽

Major Depressive ◽

Genome Wide ◽

Genetic Contributions

AbstractMajor depressive disorder and neuroticism share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression. We analysed two sets of summary statistics from genome-wide association studies of depression (from the Psychiatric Genomics Consortium and 23andMe) and compared them to GWAS of neuroticism (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only neuroticism, or with both. Second, we estimated partial genetic correlations to test whether the depression’s genetic link with other phenotypes was explained by shared overlap with neuroticism. We found evidence that most genetic variants associated with depression are likely to be shared with neuroticism. The overlapping common genetic variance of depression and neuroticism was negatively genetically correlated with cognitive function and positively genetically correlated with several psychiatric disorders. We found that the genetic contributions unique to depression, and not shared with neuroticism, were correlated with inflammation, cardiovascular disease, and sleep patterns. Our findings demonstrate that, while genetic risk factors for depression are largely shared with neuroticism, there are also non-neuroticism related features of depression that may be useful for further patient or phenotypic stratification.

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Genetics of ischemic stroke: where are we now?

Orvosi Hetilap ◽

10.1556/oh.2011.29069 ◽

2011 ◽

Vol 152 (12) ◽

pp. 455-463 ◽

Cited By ~ 1

Author(s):

Anita Maász ◽

Zoltán Szolnoki ◽

László Balikó ◽

Béla Melegh

Keyword(s):

Ischemic Stroke ◽

Genetic Variants ◽

Association Studies ◽

Renin Angiotensin System ◽

Cerebrovascular Diseases ◽

Genome Wide Association Studies ◽

Angiotensin System ◽

New Approach ◽

Genome Wide ◽

Genes Encoding

As stroke is the third leading cause of death after heart failure and tumors worldwide, cerebrovascular diseases reached substantial attention. In the past few years, significant progression has been seen in identification of genetic variants in the background of stroke and other cerebrovascular and cardiovascular events. Examination of these variants is a new approach to recognize pathogenesis of disorders that hopefully helps in future prevention and prospects of screening and, optimistically, it contributes to special care of patients susceptible for stroke. In the background of ischemic stroke several genetic variants have been identified, which localize in genes encoding proteins involved in hemostasis, renin-angiotensin system and lipid metabolism. The number of these variants exponentially increases permanently due to rapid spreading of genome wide association studies. The goal of this review is to summarize the results of genetic studies on ischemic stroke. Here the authors focus on genetic variants which can have major role in personalized medicine and prevention of stroke. Orv. Hetil., 2011, 152, 455–463.

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Pharmacogenetics and human genetic polymorphisms

Biochemical Journal ◽

10.1042/bj20100522 ◽

2010 ◽

Vol 429 (3) ◽

pp. 435-449 ◽

Cited By ~ 65

Author(s):

Ann K. Daly

Keyword(s):

Adverse Drug Reactions ◽

Molecular Basis ◽

Drug Response ◽

Genetic Factors ◽

Drug Disposition ◽

Association Studies ◽

Genome Wide Association Studies ◽

Drug Reactions ◽

Factors Affecting ◽

Genes Encoding

The term pharmacogenetics was first used in the late 1950s and can be defined as the study of genetic factors affecting drug response. Prior to formal use of this term, there was already clinical data available in relation to variable patient responses to the drugs isoniazid, primaquine and succinylcholine. The subject area developed rapidly, particularly with regard to genetic factors affecting drug disposition. There is now comprehensive understanding of the molecular basis for variable drug metabolism by the cytochromes P450 and also for variable glucuronidation, acetylation and methylation of certain drugs. Some of this knowledge has already been translated to the clinic. The molecular basis of variation in drug targets, such as receptors and enzymes, is generally less well understood, although there is consistent evidence that polymorphisms in the genes encoding the β-adrenergic receptors and the enzyme vitamin K epoxide reductase is of clinical importance. The genetic basis of rare idiosyncratic adverse drug reactions had also been examined. Susceptibility to reactions affecting skin and liver appears to be determined in part by the HLA (human leucocyte antigen) genotype, whereas reactions affecting the heart and muscle may be determined by polymorphisms in genes encoding ion channels and transporters respectively. Genome-wide association studies are increasingly being used to study drug response and susceptibility to adverse drug reactions, resulting in identification of some novel pharmacogenetic associations.

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