Hereditary Defects in Fibrinolysis Associated with Thrombosis

Hong, Jerome J.; Kwaan, Hau C.

doi:10.1055/s-2007-994934

Cited by 9 publications

(4 citation statements)

References 77 publications

(82 reference statements)

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“…Thrombotic risk has been associated with genetic variation in these three pathways (Grant 2003; Williams and Bray 2001). Mutations may directly alter components of these pathways (Hong and Kwaan 1999; Zoller et al 1997) or may indirectly alter their regulation or the proteins required for their processing (Zhang and Ginsburg 2004). Family history has long been associated with susceptibility to thrombosis, but these known mutations account for only a small portion of the variation.…”

Section: Introductionmentioning

confidence: 99%

Quantitative trait locus analysis for hemostasis and thrombosis

Hart

Hill

et al. 2008

Mamm Genome

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Susceptibility to thrombosis varies in human populations as well as many in inbred mouse strains. The objective of this study was to characterize the genetic control of thrombotic risk on three chromosomes. Previously, utilizing a tail-bleeding/rebleeding assay as a surrogate of hemostasis and thrombosis function, three mouse chromosome substitution strains (CSS) (B6-Chr5 A/J , Chr11 A/J , Chr17 A/J ) were identified (Hmtb1, Hmtb2, Hmtb3). The tailbleeding/rebleeding assay is widely used and distinguishes mice with genetic defects in blood clot formation or dissolution. In the present study, quantitative trait locus (QTL) analysis revealed a significant locus for rebleeding (clot stability) time (time between cessation of initial bleeding and start of the second bleeding) on chromosome 5, suggestive loci for bleeding time (time between start of bleeding and cessation of bleeding) also on chromosomes 5, and two suggestive loci for clot stability on chromosome 17 and one on chromosome 11. The three CSS and the parent A/J had elevated clot stability time. There was no interaction of genes on chromosome 11 with genes on chromosome 5 or chromosome 17. On chromosome 17, twenty-three candidate genes were identified in synteny

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Section: Introductionmentioning

confidence: 99%

Quantitative trait locus analysis for hemostasis and thrombosis

Hart

Hill

et al. 2008

Mamm Genome

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“…Since the blood flow impairment characterizing preeclampsia is mainly a consequence of unbalanced hemostasis, it has been suggested that defects occurring primarily in the fibrinolytic system could predispose to this obstetric complication [12,13]. Thus, inherited hypofibrinolytic mutations may constitute genetic determinants predisposing to preeclampsia.…”

Section: Introductionmentioning

confidence: 99%

Association between Plasminogen Activator Inhibitor 1 Gene Polymorphisms and Preeclampsia

Fabbro¹,

D'Elia²,

Spizzo

et al. 2003

Gynecol Obstet Invest

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It is known that the plasminogen activator inhibitor 1 (PAI-1) protein levels are increased in placentas of preeclamptic subjects. Therefore, we assessed whether polymorphisms related to the transcriptional control of the PAI-1 gene (–675 4G/5G and –844G/A) are associated with mild preeclampsia. We compared 52 women with preeclampsia to 80 women with a normal pregnancy. None of the preeclamptic women suffered from the severe form of preeclampsia. DNA was extracted from blood, and –675 4G/5G and –844G/A genotypes of the PAI-1 gene were determined. Since it has been shown that the presence of factor V Leiden, prothrombin G20210A, and MTHFR C677T gene variants may be associated with preeclampsia, their frequency was also evaluated in our study groups. The factor V Leiden, PT G20210A, and MTHFR C677T gene variants were not associated with preeclampsia. In the case of the –675 4G/5G polymorphism, genotypes 4G/4G and 5G/5G were more prevalent in the preeclamptic and in the control group, respectively. In the case of –844 G/A polymorphism, genotypes A/A and G/G were more prevalent in the preeclamptic and in the control group, respectively. By using the χ² test for trend, differences for both genotypes were significant (p = 0.0141 for the –675 genotypes and p = 0.0492 for the –844 genotypes). The frequency of the 4G and 5G alleles of the –675 gene polymorphism was significantly different between preeclamptic and normal women (p = 0.032). Differently, the allelic frequency of the –844 gene polymorphism did not show significant differences between preeclamptic and normal women (p = 0.083). In conclusion, the hypofibrinolytic genotypes 4G/4G and A/A at positions –675 and –844 of the PAI-1 gene are associated with the occurrence of mild preeclampsia independently of thrombophilic mutations of the factor V, prothrombin, and MTHFR genes.

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“…Some common situations are venous stasis, endothelial injury, and circulating activated clotting factors (9). Less often, hereditary or acquired defects of the natural anticoagulants or fibrinolytic defects are involved (10). In this study, fibrinolytic defect due to hypo/dysPLGemia was identified in about 10% of unrelated patients with deep vein thrombosis and heterozygous Ala601Thr mutations were detected in all the patients with dysPLGemia.…”

Section: Discussionmentioning

confidence: 59%

Detection of an Ala601Thr Mutation of Plasminogen Gene in 3 out of 36 Korean Patients with Deep Vein Thrombosis

2003

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Plasminogen is a key proenzyme in the fibrinolytic and thrombolytic systems. Congenital deficiency of plasminogen and molecular abnormality of plasminogen (dysplasminogenemia) have been reported in association with the thrombotic tendency in human. In dysplasminogenemia, the level of immunoreactive plasminogen is normal, although the functional activity is reduced. Human plasminogen gene spans about 52.5 kb of DNA and consists of 19 exons. Three types of mutations (Ala601Thr, Val355Phe, and Asp676Asn) have been described in dysplasminogenemia. In this study, we measured the plasminogen activity in patients with deep vein thrombosis and analyzed the DNA sequence to detect three point mutations (Ala601Thr, Val355Phe and Asp676Asn) in patients with hypo/dysplasminogenemia. Dysplasminogenemia was identified in 3 (8.3%) of unrelated 36 patients with deep vein thrombosis and the Ala601Thr mutation was detected in all three patients with dysplasminogenemia. In conclusion, dysplasminogenemia is not rare in deep vein thrombosis, which suggests a risk factor for the thrombosis in Korean population.

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Hereditary Defects in Fibrinolysis Associated with Thrombosis

Cited by 9 publications

References 77 publications

Quantitative trait locus analysis for hemostasis and thrombosis

Quantitative trait locus analysis for hemostasis and thrombosis

Association between Plasminogen Activator Inhibitor 1 Gene Polymorphisms and Preeclampsia

Detection of an Ala601Thr Mutation of Plasminogen Gene in 3 out of 36 Korean Patients with Deep Vein Thrombosis

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