Fibrinogen Gene Promoter −455 A Allele as a Risk Factor for Lacunar Stroke

Martiskainen, Mika; Pohjasvaara, Tarja; Mikkelsson, Jussi; Mäntylä, Riitta; Kunnas, Tarja; Laippala, Pekka; Ilveskoski, Erkki; Kaste, Markku; Karhunen, Pekka J.; Erkinjuntti, Timo

doi:10.1161/01.str.0000060029.23872.55

Cited by 70 publications

(61 citation statements)

References 60 publications

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“…55 On a clinical basis, it has been shown that the B␤-455 A/G polymorphism is associated with the development of coronary artery disease in type 2 diabetic subjects, independently of fibrinogen levels. 56 The same polymorphism has been related to the progression of coronary artery disease 57,58 and the development of cerebral infarcts, 59 but not in all studies (Table). 60 …”

Section: Noncoding Polymorphisms Of Fibrinogen Genementioning

confidence: 97%

Genetic and Environmental Determinants of Fibrin Structure and Function

Scott

Ariëns

Grant

2004

ATVB

138

129

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Abstract-The formation of a fibrin clot is one of the key events in atherothrombotic vascular disease. The structure of the fibrin clot and the genetic and environmental factors that modify it have effects on its biological function. Alterations in fibrin structure and function have implications for the clinical presentation of vascular disease. This review briefly describes the key features involved in the formation of a fibrin clot, its typical structure, and function. This is followed by a review of the current literature on genetic and environmental influences on fibrin structure/function and the relationship to clinical disease. Key Words: fibrin Ⅲ hemostatis Ⅲ genetic Ⅲ environment Ⅲ atherothrombosis D iseases associated with the development of thrombosis are a major cause of morbidity and mortality in the developed world. Atherothrombotic vascular disorders develop over many decades and involve the interaction of classic atherogenic risk factors such as diabetes, hyperlipidemia, and hypertension with abnormalities of the inflammatory and hemostatic systems. Arterial disease develops in a high-pressure, high-flow system, with lipid deposition and smooth muscle hyperplasia occurring to form an atherosclerotic plaque. 1 Subsequently, the plaque becomes unstable and ruptures exposing a prothrombotic lipid core activating the clotting cascade and leading to the development of a platelet-rich fibrin blood clot and arterial thrombotic occlusion. The extent of this process determines clinical outcome, ranging from no clinically noticeable event to acute coronary artery syndromes including myocardial infarction (MI), cerebrovascular and peripheral vascular disease, or sudden death. The Formation of a Fibrin ClotFibrin is the major protein constituent of the blood clot and is formed from fibrinogen, a glycoprotein that circulates largely inactively, in the blood stream. Fibrinogen consists of 6 polypeptide chains (A␣, B␤, ␥) 2 held together by disulphide bonds in a molecule with bilateral symmetry (Figure 1). The molecule consists of 3 main structural regions, 2,3 including a central region (E), which contains fibrinopeptides A and B and the amino acid termini of all 6 polypeptide chains, 2 distal regions (D) connected to the E region by 2 ␣-helical coiled segments and the D regions containing the carboxyl termini of the B␤ and ␥ chains, and those of the A␣ chain, which extend to form relatively flexible ␣C-domains, each ending in a globular domain. 2,3 In situations of tissue injury and inflammation, thrombin is generated after cleavage of prothrombin by the Xase complex. Thrombin subsequently binds to fibrinogen and cleaves the amino termini of the fibrinogen A␣ and B␤ chains at region E. This results in the release of fibrinopeptides A and B from fibrinogen, producing fibrin and initiating fibrin clot formation. Release of fibrinopeptide A by thrombin is fast and exposes a polymerization site on the E region of fibrin. 4,5 This combines with a complementary binding site on the ␥ chain in the D region of an adjac...

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Section: Noncoding Polymorphisms Of Fibrinogen Genementioning

confidence: 97%

Genetic and Environmental Determinants of Fibrin Structure and Function

Scott

Ariëns

Grant

2004

ATVB

138

129

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“…The severity SEC was shown to be increased with the elevated fibrinogen levels (8). Severe SEC, a marker of atrial stasis, is suggested to associate with thrombus formation and increased systemic embolism risk (19,25). Fibrinogen may be the key element for the development of thrombus and SEC formation.…”

Section: Discussionmentioning

confidence: 99%

“…However, these markers may change instantaneously, and they may also be affected by many other conditions. Recent studies revealed the relationship between beta-fibrinogen 455G/A polymorphism and stroke or myocardial infarction (17)(18)(19). Beta-fibrinogen 455G/A polymorphism was also shown to be associated with the increased erythrocyte aggregation and predisposing the development of stasis (28).…”

Section: Discussionmentioning

confidence: 99%

“…Previous study revealed the increased fibrinogen activity in the presence of homozygote A/A allele (14)(15)(16). It was determined that the increased A/A allele is associated with increased cardiovascular events (17,18) and increased prevalence of lacunar infarct in brain (19). However, conflicting results were also reported (20) Glycoprotein PLA1/A2 polymorphism is another gene mutation, which is responsible for predisposition to thrombosis through change in the activity of a glycoprotein IIIa receptor located on the surface of a thrombocyte.…”

Section: Introductionmentioning

confidence: 99%

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The association of beta-fibrinogen 455 G/A gene polymorphism with left atrial thrombus and severe spontaneous echo contrast in atrial fibrillation

Bozdemir¹,

Kırımlı²,

Akdeniz³

et al. 2010

Anadolu Kardiyol Derg

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Amaç: Atriyal fibrilasyonda sol atriyal trombüs oluşması açısından koagülasyon parametrelerinin rolü yeterince araştırılmamıştır. Atriyal fibrilasyonlu hastalarda sol atriyal trombüs ile veya onun öncüsü olduğu düşünülen spontan eko-kontrast varlığı (SEK) ile beta fibrinojen gen polimorfizmi ile trombosit glikoprotein IIIa gen polimorfizmi arasındaki ilişkiyi araştırmayı amaçladık. Yöntemler: Transözofageal ekokardiyografi yapılan atriyal fibrilasyonlu 47 hasta enine kesitsel gözlemsel çalışmamıza dahil edildi. Hastalar 2 gruba ayrıldı. Sol atriyal trombüsü olanlar Grup 1'i (n=24) ve trombüsü olmayanlar grup 2'yi (n=23) oluşturdu. Beta fibrinojen gene polimorfizm veya glikoprotein IIIa gen polimorfizmlerini saptamak için genetik analizler yapıldı. İstatistiksel analizde Mann Whitney U ve Ki-kare testleri kullanıldı. Bulgular: Demografik ve klinik özellikler bakımından gruplar arasında fark saptanmadı. Beta fibrinojen 455 G/A gen polimorfizm sıklığı grup 1'de (%37.5) grup 2'ye göre (%15) istatistiksel anlamlılığa ulaşmayacak şekilde (p=0.23) daha yüksek saptandı. Çalışma grubuna ciddi SEK'i olan hastalar da eklendiğinde (trombüs ve ciddi SEK n=27) 2 grup arasındaki fark (%44.4-%10) istatistiksel anlamlılığa ulaşmaktaydı (p=0.01). Glikoprotein IIIa Pl A1/A2 polimorfizmi ise gruplar arasında (p=0.73) SEK eklense de (p=0.82) farklı bulunmadı. Grup I'de grup II'ye göre mitral yetmezliği skoru daha düşük olma eğiliminde (p=0.08), SEK skoru ise anlamı olarak daha yüksek idi (p=0.03). ÖZETOb jec ti ve: The role of coagulation parameters left atrial thrombus formation in atrial fibrillation has not been investigated before. We aimed to investigate the association between the beta-fibrinogen gene polymorphism or glycoprotein IIIa gene polymorphism and presence of left atrial (LA) thrombus or spontaneous echo contrast (SEC) in patients with atrial fibrillation (AF). Methods: Forty-seven patients with AF, in whom transesophageal echocardiography was performed, were included to this cross-sectional observational study. Patients were divided in two groups; those with LA thrombus (n=24) were assigned to group 1 and those without thrombusin group 2 (n=23). DNA analysis was conducted to determine gene polymorphism in all patients. Mann-Whitney U test or Chi-square tests were used for statistical analysis Results: There were no significant differences between groups regarding to demographic and clinical characteristics. The frequency of betafibrinogen 455 G/A polymorphism was higher (37.5%) in group 1 as compared to group 2 (15.1%) but it did not reach statistical difference (p=0.23). When we added patients with severe SEC in the study group (patients with severe SEC and/or thrombus n=27) the difference (44.40%-10%) reached the statistical difference (p=0.01). Glycoprotein IIIa Pl A1/A2 polymorphism was not different between groups with (p=0.82) or without SEC (p=0.73). Conclusion: In patients with atrial fibrillation, beta-fibrinogen 455 G/A gene polymorphism is associated with the presence of left atrial thrombus and severe SEC...

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“…Concentrações plasmáticas elevadas de fibrinogênio foram associadas a maior risco de eventos vasculares como: TVE, doença arterial coronariana e infarto cerebral (Martiskainen et al, 2003;Chen et al, 2008;Bozdemir et al, 2010). Polimorfismos nos genes das cadeias α, β e γ foram associados com o aumento da concentração de fibrinogênio plasmático (De Maat et al, 1998;De Maat, 2001;Manocha et al, 2007;Jacquemin et al, 2008;Siegerink, Rosendaal e Algra, 2009).…”

Section: Polimorfismo No Gene Da Cadeia β Do Fibrinogênio (Fgb -455g>unclassified

Polimorfismos genéticos relacionados à hemostasia e a sua relação com abortos espontâneos recorrentes

Bertinato¹

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Fibrinogen Gene Promoter −455 A Allele as a Risk Factor for Lacunar Stroke

Cited by 70 publications

References 60 publications

Genetic and Environmental Determinants of Fibrin Structure and Function

Genetic and Environmental Determinants of Fibrin Structure and Function

The association of beta-fibrinogen 455 G/A gene polymorphism with left atrial thrombus and severe spontaneous echo contrast in atrial fibrillation

Polimorfismos genéticos relacionados à hemostasia e a sua relação com abortos espontâneos recorrentes

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