Plasminogen activator inhibitor-1 gene 4G/5G polymorphism in cancer patients with and without thrombosis

Eroğlu, Aydan; Ulu, Arzu; Akar, Nejat

doi:10.1007/s11239-006-9054-z

Cited by 13 publications

(9 citation statements)

References 9 publications

(3 reference statements)

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“…The 4G/4G genotype confers an increase in the risk of mortality in adult patients with septic shock due to a greater organ failure, and it is also associated with higher IL‐1, TNF‐α, and PAI‐1 plasma concentration and increased severity in these patients [68]. PAI‐1 may play an important role in growth, angiogenesis, and metastasis of some types of tumours such as prostate cancer and breast cancer [69, 70]. The 4G/4G genotype is also significantly associated with increased risk of myocardial infarction [71], arterial hypertension [72], early onset of coronary heart disease [73], and pneumonia [63].…”

Section: The 4g/5g Polymorphism Of the Plasminogen Activator Inhibitomentioning

confidence: 99%

“…The 4G allele renders higher PAI‐1 expression in response to IL‐1 [56, 57], angiotensin II [64], very low density lipoproteins [65], and circadian clock protein heterodimers BMAL/CLOCK [69] than the 5G allele. In stimulated human MC line HMC‐1 cells, the transcriptional activity of 4G‐PAI‐1 promoter was 32% higher than 5G‐PAI‐1 promoter ( P <0.001), whereas their promoter activities were comparable in resting cells [80].…”

Section: The 4g/5g Polymorphism Of the Plasminogen Activator Inhibitomentioning

confidence: 99%

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Plasminogen activator inhibitor‐1 and asthma: role in the pathogenesis and molecular regulation

Paek

2009

Clin Experimental Allergy

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Plasminogen activator inhibitor (PAI)-1 is a major inhibitor of the fibrinolytic system. PAI-1 levels are markedly increased in asthmatic airways, and mast cells (MCs), a pivotal cell type in the pathogenesis of asthma, are one of the main sources of PAI-1 production. Recent studies suggest that PAI-1 may promote the development of asthma by regulating airway remodelling, airway hyperresponsiveness (AHR), and allergic inflammation. The single guanosine nucleotide deletion/insertion polymorphism (4G/5G) at -675 bp of the PAI-1 gene is the major genetic determinant of PAI-1 expression. Plasma PAI-1 level is higher in people with the 4G/4G genotype than in those with the 5G/5G genotype. A strong association between the 4G/5G polymorphism and the risk and the severity of asthma has been suggested. Levels of plasma IgE and PAI-1 and severity of AHR are greater in asthmatic patients with the 4G/4G genotype than in those with the 5G/5G genotype. The PAI-1 promoter with the 4G allele renders higher transcription activity than the PAI-1 promoter with the 5G allele in stimulated MCs. The molecular mechanism for the 4G allele-mediated higher PAI-1 expression is associated with greater binding of upstream stimulatory factor-1 to the E-box adjacent to the 4G site (E-4G) than to the E-5G. In summary, PAI-1 may play an important role in the pathogenesis of asthma. Further studies evaluating the mechanisms of PAI-1 action and regulation may lead to the development of a novel prognostic factor and therapeutic target for the treatment and prevention of asthma and other PAI-1-associated diseases.

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Section: The 4g/5g Polymorphism Of the Plasminogen Activator Inhibitomentioning

confidence: 99%

Section: The 4g/5g Polymorphism Of the Plasminogen Activator Inhibitomentioning

confidence: 99%

Plasminogen activator inhibitor‐1 and asthma: role in the pathogenesis and molecular regulation

Paek

2009

Clin Experimental Allergy

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“…Cancers were confirmed histologically or pathologically in most studies. Controls were mainly matched on sex and age, of which 17 were hospital based [21], [22], [23], [24], [29], [30], [31], [32], [33], [35], [36], [37], [38], [40], [41], [42], [43], 8 were population based [20], [25], [26], [27], [28], [34], [39]. Furthermore, 10 studies were conducted with subjects >500 in both case and control groups [20], [25], [26], [27], [28], [29], [34], [39], [40].…”

Section: Resultsmentioning

confidence: 99%

“…Many molecular epidemiological studies have been conducted to investigate the association between 4G/5G polymorphism and cancer risk in humans [20]–[43]. However, the results from these studies are to some extent divergent, but nevertheless intriguing, which may be owe to limitations in individual studies.…”

Section: Introductionmentioning

confidence: 99%

PAI-1 4G/5G Polymorphism Contributes to Cancer Susceptibility: Evidence from Meta-Analysis

Wang

Cao

Wang³

et al. 2013

PLoS ONE

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BackgroundThe plasminogen activator inhibitor-1 (PAI-1) is expressed in many cancer cell types and allows the modulation of cancer growth, invasion and angiogenesis. To date, studies investigated the association between a functional polymorphism in PAI-1 (4G/5G) and risk of cancer have shown inclusive results.MethodsA meta-analysis based on 25 case-control studies was performed to address this issue. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with I2 test.ResultsOverall, a significant increased risk of cancer was associated with the PAI-1 4G/4G polymorphism for the allele contrast (4G vs. 5G: OR = 1.10, CI = 1.03–1.18, I2 = 49.5%), the additive genetic model (4G/4G vs. 5G/5G: OR = 1.21, CI = 1.06–1.39, I2 = 51.9%), the recessive genetic model (4G/4G vs. 4G/5G+5G/5G: OR = 1.11, CI = 1.04–1.18, I2 = 20.8%). In the subgroup analysis by ethnicity, the results indicated that individuals with 4G/4G genotype had a significantly higher cancer risk among Caucasians (4G/4G vs. 5G/5G: OR = 1.31, 95%CI = 1.09–1.59, I2 = 59.6%; 4G/4G vs. 4G/5G: OR = 1.12, 95%CI = 1.04–1.21, I2 = 3.6%; recessive model: OR = 1.12, 95%CI = 1.05–1.21, I2 = 25.3%).ConclusionsThe results of the present meta-analysis support an association between the PAI-1 4G/5G polymorphism and increasing cancer risk, especially among Caucasians, and those with 4G allele have a high risk to develop colorectal cancer and endometrial cancer.

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“…Choudhury and friends detected that the free PAI-1 levels can be significant venous occlusion in TAO patients [17]. This gene mutation accused in Turkish DVT patients [18]. A meta-analyze signs to 4G/4G genotype was 20% folds increased of myocardial infarction risk that have included 9 studies [19].…”

Section: Discussionmentioning

confidence: 99%

Association of the plasminogen activator inhibitor-1(PAI-1) gene 4G/5G promoter polymorphism in Buerger's disease (Tromboangiitis obliterans)

Manduz¹,

Katrancioglu²,

Karahan³

et al. 2010

Health

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Thromboangiitis obliterans (TAO) is an unusual tobacco-associated vasculopathy that is a non- atherosclerotic inflammatory disorder of unkn- own etiology that affects small and medium- sized vessels of the extremities. The single guanosine nucleotide deletion/insertion polym- orphism (4G/5G) at -675 bp in promoter region of the PAI-1 gene is the major genetic determi- nant of PAI-1 expression. Plasma PAI-1 level is higher in people with the homozygous 4G genotype than in those with the 5G/5G genotype and renders higher transcription activity. The aim of this study was to determine the status and the role of PAI-1 gene 4G/5G promoter polymorphism in patients with Buerger's disease (Thromboangiitis obliterans—TAO). The current case-control study included 30 consecutive pat- ients with Buerger's disease (mean age 42.9 ± 14.3 years, 28 men and 2 women), and 30 healthy volunteers (mean age 40.9 ± 4.79 years, 27 men and 3 women) between January 2006 and September 2009. Patients and control cases were genotyped for the 4G/5G polymorphism using the multiplex PCR based stripassay reverse hybridisation technique. It was found that heterozygote PAI-1 gene polymorphisms (p < 0.05) was significantly more frequent in patients with TAO in the current results. There was a significant difference in genotype distribution between the two groups (P < 0.001). The 4G allele occurred more frequently in the patient group of heavy smokers (P = 0.05). The current study shows the higher prevalence of of 4G allele in TAO patients in Sivas population means gene may predispose to TAO

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Plasminogen activator inhibitor-1 gene 4G/5G polymorphism in cancer patients with and without thrombosis

Cited by 13 publications

References 9 publications

Plasminogen activator inhibitor‐1 and asthma: role in the pathogenesis and molecular regulation

Plasminogen activator inhibitor‐1 and asthma: role in the pathogenesis and molecular regulation

PAI-1 4G/5G Polymorphism Contributes to Cancer Susceptibility: Evidence from Meta-Analysis

Association of the plasminogen activator inhibitor-1(PAI-1) gene 4G/5G promoter polymorphism in Buerger's disease (Tromboangiitis obliterans)

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