scholarly journals Association between Five Common Plasminogen Activator Inhibitor-1 (PAI-1) Gene Polymorphisms and Colorectal Cancer Susceptibility

2020 ◽  
Vol 21 (12) ◽  
pp. 4334 ◽  
Author(s):  
Jisu Oh ◽  
Hui Jeong An ◽  
Jung Oh Kim ◽  
Hak Hoon Jun ◽  
Woo Ram Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Plasminogen Activator ◽  
Gene Polymorphisms ◽  
Cancer Susceptibility ◽  
Plasminogen Activator Inhibitor ◽  
Cell Types ◽  
Plasminogen Activator Inhibitor 1 ◽  
Polymerase Chain ◽  
Activator Inhibitor ◽  
Pai 1

The plasminogen activator inhibitor-1 (PAI-1) is expressed in many cancer cell types and modulates cancer growth, invasion, and angiogenesis. The present study investigated the association between five PAI-1 gene polymorphisms and colorectal cancer (CRC) risk. Five PAI-1 polymorphisms (−844G > A [rs2227631], −675 4G > 5G [rs1799889], +43G > A [rs6092], +9785G > A [rs2227694], and +11053T > G [rs7242]) were genotyped using a polymerase chain reaction-restriction fragment length polymorphism assay in 459 CRC cases and 416 controls. Increased CRC risk was more frequently associated with PAI-1 −675 5G5G polymorphism than with 4G4G (adjusted odds ratio (AOR) = 1.556; 95% confidence interval (CI): 1.012–2.391; p = 0.04). In contrast, for the PAI-1 +11053 polymorphism, we found a lower risk of CRC with the GG genotype (AOR = 0.620; 95% CI: 0.413–0.932; p = 0.02) than with the TT genotype, as well as for recessive carriers (TT + TG vs. GG, AOR = 0.662; 95% CI: 0.469–0.933; p = 0.02). The +43AA genotype was associated with lower overall survival (OS) than the +43GG genotype. Our results suggest that the PAI-1 genotype plays a role in CRC risk. This is the first study to identify an association between five PAI-1 polymorphisms and CRC incidence worldwide.

scholarly journals Role of plasminogen activator inhibitor-1 gene polymorphisms in osteoporosis: A study in Chinese post-menopausal women

2018 ◽  
Vol 16 ◽  
pp. 205873921876729
Author(s):  
An Wan ◽  
Daodong Liu
Keyword(s):  
Gene Polymorphisms ◽  
Chinese Women ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Post Menopausal ◽  
Activator Inhibitor ◽  
Pai 1

Osteoporosis is a chronic multifactorial disease characterized by deterioration of bone mass and is vulnerable to bone fracture. Plasminogen activator inhibitor-1 (PAI-1) is an important molecule for maintenance of optimum bone mass. Several single-nucleotide polymorphisms (SNPs) in PAI-1 have been reported to alter PAI-1 expression and/or the translational level. In this report, we explored the possible role of common PAI-1 gene polymorphisms on predisposition to osteoporosis in a Chinese cohort. A total of 364 post-menopausal Chinese women diagnosed of having osteoporosis and 350 healthy females hailing from similar areas were enrolled in this study. Five common SNPs (−844G > A, −6754G/5G, +43G > A, +9785G > A and +11053T > G) were genotyped by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). Relative expression of PAI-1 mRNA and plasma PAI-1 levels were quantified by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Prevalence of homozygous mutant (5G/5G) and minor allele (5G) of PAI-1 (−675 4G/5G) polymorphism was significantly more frequent in patients than in healthy controls (5G/5G: P < 0.0001, odds ratio (OR) = 3.18; 5G: P < 0.0001, OR = 1.65). Both plasma PAI-1 and relative mRNA expression levels were significantly lower in patients compared to healthy controls. Interestingly, the quantity of plasma PAI-1 and mRNA expression was correlated with PAI-1 (−675 4G/5G) polymorphism: subjects with 4G/4G genotype had elevated PAI-1 in comparison to homozygous mutant, and displayed lower quantity of PAI-1 protein and mRNA values. PAI-1 (−675 4G/5G) mutant is associated with susceptibility to development of osteoporosis in post-menopausal Chinese women. Furthermore, this variant in the promoter region alters plasma protein levels and relative expression of PAI-1.

Genetic association of five plasminogen activator inhibitor-1 (PAI-1) polymorphisms and idiopathic recurrent pregnancy loss in Korean women

2013 ◽  
Vol 110 (10) ◽  
pp. 742-750 ◽  
Author(s):  
Bo Eun Lee ◽  
Yi Seul Choi ◽  
Ji Hyang Kim ◽  
Ji Eun Shin ◽  
HyungChul Rah ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Plasminogen Activator Inhibitor ◽  
Korean Women ◽  
Plasminogen Activator Inhibitor 1 ◽  
Ordinal Logistic Regression Analysis ◽  
Polymerase Chain ◽  
Activator Inhibitor ◽  
Pai 1

SummaryPlasminogen activator inhibitor-1 (PAI-1) is important for maintaining pregnancy. Aberrantly increased PAI-1 levels may contribute to thrombosis and inflammation, leading to pregnancy loss. This study investigated the association of PAI-1 polymorphisms (PAI-1 rs2227631 [-844G>A], rs1799889 [-675 4G/5G], rs6092 [43G>A], rs2227694 [9785G>A], and rs7242 [11053T>G]) with idiopathic recurrent pregnancy loss (RPL) in Korean women. We screened 308 RPL patients and 227 control participants for five PAI-1 polymorphisms. Genotyping of PAI-1 was performed by polymerase chain reaction-restriction fragment length polymorphism assay. PAI-1 4G4G and -844AA/ 4G4G/11053GG genotypes were associated with RPL. PAI-1 -844A/4G/43G/9785G/11053G haplotype was connected to hypofibrinolytic status (i.e. increased levels of plasma PAI-1, increased numbers of platelets, reduced prothrombin time, and reduced activated partial thromboplastin time). Moreover, PAI-1 11053TG+GG frequency was positively related to plasma homocysteine and urate levels, whereas -844AA frequency was associated with plasma folate concentrations according to ordinal logistic regression analysis. Based on these results, we propose that PAI-1 -844G>A, 4G/5G, and 11053T>G polymorphisms are markers of RPL.

scholarly journals Combined presence of coagulation factor XIII V34L and plasminogen activator inhibitor 1 4G/5G gene polymorphisms significantly contribute to recurrent pregnancy loss in serbian population

2019 ◽  
Vol 0 (0) ◽  
Author(s):  
Ivana Joksic ◽  
Zeljko Mikovic ◽  
Dejan Filimonovic ◽  
Jelena Munjas ◽  
Natasa Karadzov Orlic ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Gene Polymorphisms ◽  
Factor Xiii ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
History Of ◽  
Activator Inhibitor ◽  
Pai 1

SummaryBackgroundRecurrent pregnancy loss (RPL) is a heterogeneous condition affecting up to 5% of women of reproductive age. Inherited thrombophilia have been postulated as one of the causes of RPL. Here we examined the prevalence of nine thrombophilic gene polymorphisms among women with history of recurrent miscarriages and fertile controls.MethodsThe study included 70 women with history of at least three early pregnancy losses and 31 fertile controls with no miscarriages. We investigated mutations in genes responsible for clotting and fibrinolysis, including factor V (FV) Leiden, FV H1299R, factor II (FII) G20210A, methylene tetrahydrofolate reductase (MTHFR) C677T and A1298C, factor XIII (FXIII) V34L, plasminogen activator inhibitor-1 (PAI-1) 4G/5G and endothelial protein C receptor (EPCR) H1 and H3 haplotypes using reverse polymerase chain reaction ViennaLab cardiovascular disease StrippAssays.ResultsOur results showed no significant increase in prevalence of tested polymorphisms in women with RPL. However, relative risk for PRL among women heterozygous for FXIII V34L was 2.81 times increased (OR 2.81, 95% CI 1.15–6.87, P=0.023). Haplotype analysis showed that combined presence of high-risk genotypes for FXIII and PAI-1 significantly increases risk for RPL (OR 13.98, CI 95% 1.11–17.46, P=0.044).ConclusionsThis is the first study in Serbian population that investigated prevalence of FVR2, A1298C, FXIII V34L and EPCR gene variants. Compound heterozygosity for FXIII V34L and PAI-1 4G is significant risk factor for recurrent miscarriage. Our results should be viewed in context of small case-control study, so further large prospective studies are need for confirmation of our findings.

scholarly journals Plasminogen activator inhibitor-1 and haemostasis in obesity

2001 ◽  
Vol 60 (3) ◽  
pp. 341-347 ◽  
Author(s):  
Nicola J. Mutch ◽  
Heather M. Wilson ◽  
Nuala A. Booth
Keyword(s):  
Adipose Tissue ◽  
Plasminogen Activator ◽  
Transforming Growth Factor ◽  
Plasminogen Activator Inhibitor ◽  
Cell Types ◽  
Plasminogen Activator Inhibitor 1 ◽  
Increased Risk ◽  
Human Material ◽  
Activator Inhibitor ◽  
Pai 1

The connection between obesity and disordered haemostasis is well established, but incompletely understood. There is a strong link between inhibition of fibrinolysis and obesity, and elevation of the plasma inhibitor, plasminogen activator inhibitor-1 (PAI-1), is regarded as a central factor. Here we explore the increased risk of atherothrombotic disorders in obese subjects, and the evidence for metabolic and genetic causes. There is a clear relationship between plasma PAI-1 and obesity, and adipose tissue synthesises PAI-1, as has been shown in mouse and rat models, and more recently in human material. This tissue also produces several effector molecules that can up regulate PAI-1. These molecules include transforming growth factor b, tumour necrosis factor a, angiotensin II and interleukin 6, all of which up regulate PAI-1 in various cell types. The issue of whether adipose tissue directly contributes to plasma PAI-1, or whether it primarily contributes indirectly, its products stimulating other cells to produce PAI-1 that feeds into the plasma pool, is not yet resolved. Finally, we briefly examine other proteins of haemostasis that are products of adipose tissue. Further studies are needed to define the regulation of these proteins, in adipose tissue itself and in other cells influenced by its products, in order to extend recent insights into the links between obesity and haemostasis.

scholarly journals Plasminogen activator inhibitor 1 (PAI-1) 1334G/A genetic polymorphism in colorectal cancer.

2003 ◽  
Vol 50 (2) ◽  
pp. 489-495 ◽  
Author(s):  
Beata Smolarz ◽  
Hanna Romanowicz-Makowska ◽  
Andrzej Kulig
Keyword(s):  
Colorectal Cancer ◽  
Plasminogen Activator ◽  
Pcr Amplification ◽  
Plasminogen Activator Inhibitor ◽  
Cancer Tissue ◽  
Plasminogen Activator Inhibitor 1 ◽  
Gene Encoding ◽  
Gene Variability ◽  
Activator Inhibitor ◽  
Pai 1

Plasminogen activator inhibitor 1 (PAI-1) content in colorectal cancer tissue extracts may be of strong prognostic value: high levels of PAI-1 in tumours predict poor prognosis. The gene encoding PAI-1 is highly polymorphic and PAI-1 gene variability could contribute to the level of PAI-1 biosynthesis. In the present work the distribution of genotypes and frequency of alleles of the 1334G/A polymorphism in 92 subjects with colorectal cancer in samples of cancer tissue and distant mucosa samples as well as in blood were investigated. Blood samples age matched healthy individuals (n = 110) served as control. The 1334G/A polymorphism was determined by PCR amplification using allele specific primers. No differences in the genotype distributions and allele frequencies between blood, distant mucosa samples and cancer tissue were detected. However, the distribution of the genotypes of the 1334G/A polymorphism in patients differed significantly (P

scholarly journals Plasminogen activator inhibitor-1 impairs plasminogen activationmediated vascular smooth muscle cell apoptosis

2006 ◽  
Vol 96 (11) ◽  
pp. 665-670 ◽  
Author(s):  
Patrick Rossignol ◽  
Eduardo Anglès-Cano ◽  
Henri Lijnen
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Cell Types ◽  
Plasminogen Activation ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

SummaryThe role of plasminogen activator inhibitor-1 (PAI-1) in vascular smooth muscle cell (VSMC) apoptosis mediated by plasminogen activation was studied with the use of aorticVSMC derived from mice with deficiency of PAI-1 (PAI-1-/-), tissue-type (t-PA-/-) or urokinase-type (u-PA-/-) plasminogen activator or from wildtype (WT) mice with corresponding genetic background. Plasminogen incubated with confluentVSMC was activated ina concentration-dependent and saturable manner for all four cell types, with maximal activation rates that were comparable for WT,u-PA-/and t-PA-/cells,but about two-fold higher for PAI-1-/cells. Plasminogen activation was impaired by addition of the lysine analogue 6-aminohexanoic acid, and by addition of t-PA and u-PA neutralizing antibodies, suggesting that it depends on binding to cell surface COOH-terminal lysine residues, and on plasminogen activator activity. Morphological alterations consistent with apoptosis were observed much earlier in PAI-1-/than in WT VSMC. Without addition of plasminogen, the apoptotic index was similar for all four cell types, whereas after incubation with physiological plasminogen concentrations, it was greater in PAI-1-/VSMC, as compared to WT, t-PA-/or u-PA-/VSMC. Furthermore, the apoptotic rate paralleled the release of plasmin. Thus, plasmin-mediated apoptosis of VSMC occurs via plasminogen activation by either t-PA or u-PA and is impaired by PAI-1.

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