Evaluating the Genetic Component of Ischemic Stroke Subtypes

Jerrard-Dunne, Paula; Cloud, Geoffrey; Hassan, Ahamad; Markus, Hugh S.

doi:10.1161/01.str.0000069723.17984.fd

Cited by 210 publications

(200 citation statements)

References 23 publications

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“…This is consistent with previous observations, such as differential associations between family history and specific stroke subtypes, 3 and the finding that most monogenic causes of stroke predispose to a single subtype. 44 GWASs have now provided convincing support for this hypothesis.…”

Section: Insights Into Stroke Pathophysiologysupporting

confidence: 93%

“…[2][3][4] Family history data suggest that genetic predisposition differs by subtype of stroke, with greater familial associ ations for large-artery and small-artery (lacunar) stroke than for cardio embolic stroke. 3 These data also indicate that stroke and coronary artery disease share genetic factors, as a family history of coronary artery disease is associated with an increased risk of large-artery stroke, 5 and a family history of stroke is associated with acute coronary syndrome. 6 Furthermore, a family history of stroke is also strongly associated with risk factors for stroke, such as hypertension and diabetes mellitus, which makes it important to determine whether any identified genetic factors predispose patients to stroke indirectly via risk factors, or independently of the risk factors.…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms and treatment of ischaemic stroke—insights from genetic associations

Markus

Bevan

2014

Nat Rev Neurol

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| The precise pathophysiology of ischaemic stroke is unclear, and a greater understanding of the different mechanisms that underlie large-artery, cardioembolic and lacunar ischaemic stroke subtypes would enable the development of more-effective, subtype-specific therapies. Genome-wide association studies (GWASs) are identifying novel genetic variants that associate with the risk of stroke. These associations provide insight into the pathophysiological mechanisms, and present opportunities for novel therapeutic approaches. In this Review, we summarize the genetic variants that have been linked to ischaemic stroke in GWASs to date and discuss the implications of these associations for both our understanding and treatment of ischaemic stroke. The majority of genetic variants identified are associated with specific subtypes of ischaemic stroke, implying that these subtypes have distinct genetic architectures and pathophysiological mechanisms. The findings from the GWASs highlight the need to consider whether therapies should be subtype-specific. Further GWASs that include large cohorts are likely to provide further insights, and emerging technologies will complement and build on the GWAS findings.

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Section: Insights Into Stroke Pathophysiologysupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Mechanisms and treatment of ischaemic stroke—insights from genetic associations

Markus

Bevan

2014

Nat Rev Neurol

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“…Evidence shows that genetic factors are more important in small-and large-vessel stroke than in cardio-embolic stroke [8,9] . Some intermediate phenotypes also exhibit high heritability, such as carotid intima-medial wall thickness (IMT) and white-matter lesions (WML) [3] .…”

Section: Ischemic Strokementioning

confidence: 99%

Genetics of stroke

Guo

Liu

2010

Acta Pharmacol Sin

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Stroke is the second most common cause of death and the most common cause of disability in developed countries. Stroke is a multifactorial disease caused by a combination of environmental and genetic factors. Numerous epidemiologic studies have documented a significant genetic component in the occurrence of strokes. Genes encoding products involved in lipid metabolism, thrombosis, and inflammation are believed to be potential genetic factors for stroke. Although a large group of candidate genes have been studied, most of the epidemiological results are conflicting. Studies of stroke as a monogenic disease have made huge progress, and animal models serve as an indispensable tool to dissect the complex genetics of stroke. In the present review, we provide insight into the role of in vivo stroke models for the study of stroke genetics.

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“…Hipertansiyon, endotel disfonksiyonu meydana getirerek ve endotelin lipoproteinlere geçirgenliğini artırarak ateroskleroz oluşumunu arttırmaktadır 21 . Diabetes mellitus iskemik inme için bağımsız risk faktörüdür.…”

Section: Gereç Ve Yöntemunclassified

Determination of Prothrombotic Gene Polymorphisms and Stroke Risk Factors in Young Ischemic Stroke Patients

Demir¹,

Atis²,

Özel³

et al. 2014

Sakarya Med J

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Genç iskemik inmeli hastalarda MTHFR C677T, Protrombin G20210A ve Faktör V Leiden (G1691A) gen polimorfizmlerinin bir risk faktörü olup olmadığının araştırılmasıdır. Gereç ve yöntem: Çalışmaya, 50 yaş altında iskemik strok geçirmiş 142 hasta ve 101 kontrol grubu (sağlıklı poliklinik hastası) toplam 243 kişi dahil edildi. Hasta ve kontrol grubundan EDTA'lı tüplere periferik venöz kan örnekleri alındı ve genomik deoksiribonükleik asitler (DNA) elde edildi. Faktör V Leiden, FII G20210A ve MTHFR C677T polimorfizmleri standart Real Time -PCR protokolü ile genotiplemesi yapıldı. Hastaların yatışının 1. ve 3. günleri beyin görüntülemesi yapıldı. İstatistiksel olarak ki-kare, anova testi ve logistik regresyon analizi kullanıldı. Bulgular: Çalışma, 142'si (58,4%) arteryal iskemik strok hastalarından ve 101'i (41,6%) sağlıklı kontrol grubundan oluşmaktaydı. Arteryel iskemik strok hastalarda kontrol grubuna göre daha fazla MTHFR C677T mutasyonu vardı (p<0,05). MTHFR geninin heterozigot olması strok geçirme ihtimalini bağımsız olarak 2 kat arttırmaktadır. Çalışmamızda MTHFR geninin homozigot olması bir hastanın strok geçirmesi için bağımsız risk faktörü olarak bulunmamıştır. Sonuç: Genç iskemik inme etiyopatogenezinde protrombotik gen mutasyonlarının rolü vardır.

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Evaluating the Genetic Component of Ischemic Stroke Subtypes

Cited by 210 publications

References 23 publications

Mechanisms and treatment of ischaemic stroke—insights from genetic associations

Mechanisms and treatment of ischaemic stroke—insights from genetic associations

Genetics of stroke

Determination of Prothrombotic Gene Polymorphisms and Stroke Risk Factors in Young Ischemic Stroke Patients

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