Polymorphism Of Plasminogen Activator Inhibitor-1 Gene Research Articles

PAI-1 genetic polymorphisms influence septic patients' outcomes by regulating neutrophil activity.

Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathophysiology of sepsis, but the exact mechanism remains debatable. In this study, we investigated the associations among the serum levels of PAI-1, the incidence of 4G/5G promoter PAI-1 gene polymorphisms, immunological indicators, and clinical outcomes in septic patients. A total of 181 patients aged 18-80 years with sepsis between November 2016 and August 2018 in the intensive care unit in the Xinhua Hospital were recruited in this retrospective study, with 28-day mortality as the primary outcome. The initial serum level of PAI-1 and the presence of rs1799768 single nucleotide polymorphisms (SNPs) were examined. Univariate logistic regression and multivariate analyses were performed to determine the factors associated with different genotypes of PAI-1, serum level of PAI-1, and 28-day mortality. The logistic analysis suggested that a high serum level of PAI-1 was associated with the rs1799768 SNP of PAI-1 (4G/4G and 4G/5G) (Odds ratio [OR]: 2.49; 95% confidence interval [CI]: 1.09, 5.68). Furthermore, a high serum level of PAI-1 strongly influenced 28-day mortality (OR 3.36; 95% CI 1.51, 7.49). The expression and activation of neutrophils (OR 0.96; 95% CI 0.93, 0.99), as well as the changes in the expression patterns of cytokines and chemokine-associated neutrophils (OR: 1.00; 95% CI: 1.00, 1.00), were both regulated by the genotype of PAI-1. Genetic polymorphisms of PAI-1 can influence the serum levels of PAI-1, which might contribute to mortality by affecting neutrophil activity. Thus, patients with severe sepsis might clinically benefit from enhanced neutrophil clearance and the resolution of inflammation via the regulation of PAI-1 expression and activity.

Family-based analysis of -675 4G/5G polymorphism in the PAI-1 gene of polycystic ovary syndrome in Chinese population

Previous studies have shown that 4G/5G polymorphism in promoter region of plasminogen activator inhibitor-1 (PAI-1) gene can affect insulin sensitivity by elevating the level and activity of plasma PAI-1. In order to elucidate the relationship between the polymorphism of PAI-1 gene and polycystic ovary syndrome (PCOS), we used transmission disequilibrium test (TDT) to study the family of PCOS. Eight hundred and fifty-five participants consisting of 285 trios (mother, father and offspring with PCOS) were recruited at the Center of Reproductive Medicine, Shandong University from July 2007 to August 2014. 4G/5G polymorphism of PAI-1 gene was genotyped using direct sequencing protocol and TDT was used to analyse the association between PAI-1 gene and PCOS. Though the 5G allele in PAI-1 gene was overtransmitted in families, no statistical significance existed and there was no association between PAI-1 gene and PCOS, indicating that PAI-1 gene was unlikely to play a major role in the aetiology of PCOS in Chinese population. Impact Statement What is already known on this subject? Some studies have shown that 4G/5G polymorphism in promoter region of plasminogen activator inhibitor-1 (PAI-1) gene can affect insulin sensitivity by elevating the level and activity of plasma PAI-1, participating in the formation of insulin resistance (IR). What do the results of this study add? Though the 5G allele in PAI-1 gene was overtransmitted in families, no statistical significance existed and there was no association between PAI-1 gene and polycystic ovary syndrome (PCOS). What are the implications of these findings for clinical practice and/or further research? PAI-1 gene was unlikely to play a major role in the aetiology of PCOS.

Association between plasminogen activator inhibitor-1 gene polymorphisms and susceptibility to Parkinson's disease in Chinese patients.

Parkinson's disease (PD) is a neurodegenerative disease that usually leads to memory impairment, cognitive decline and dementia. Previous studies have reported that plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms play important roles in cardiovascular diseases, obesity, inflammation and other diseases. However, the role of PAI-1 in the diagnosis of Parkinson's disease has not been reported so far. This study was a case-control study. This study included 131 PD patients and 97 healthy volunteers. polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze the polymorphic loci of five different regions in PAI-1 gene (rs2227631, rs1799889, rs6092, rs2227694 and rs7242). 60 PD patients and 60 healthy volunteers were selected to detect the plasma PAI-1 concentration. The allele and genotype frequencies of SNPs were assessed using the SHEsis program. We found that GG genotype frequency and G allele frequency of rs2227631 was significantly higher in the PD patients. Statistically significant difference for rs1799889 could be observed in overdominant model. In subgroup analysis, a significant difference in genotype frequency distribution and allele frequency was found for rs2227631 and rs1799889 between early-onset PD group and the control group. For cognitive dysfunction, the subcomponent showed that GG genotype frequency and G allele frequency of rs2227631 was significantly higher in normal cognition group. The codominant model of rs1799889 was significantly different between the cognitive impairment group and the control group. In addition, the expression of PAI-1 in plasma of PD patients was significantly higher than that of controls, and further analysis showed that the expression of PAI-1 in patients with cognitive impairment was significantly higher than that in patients with cognitive normal. Our results indicate that the PAI-1 gene rs2227631 and rs1799889 polymorphisms were significantly associated with PD susceptibility in the Chinese Han population. PAI-1 has the potential to become a new therapeutic target and diagnostic marker.

Plasminogen Activator Inhibitor-1 (PAI-1) Gene Polymorphisms Associated with Cardiovascular Risk Factors Involved in Cerebral Venous Sinus Thrombosis.

Cerebral venous sinus thrombosis (CVST), accounting for less than 1% of stroke cases, is characterized by various causes, heterogeneous clinical presentation and different outcome. The plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms has been found to be associated with CVST. The aim of this retrospective study was to determine the potential association of PAI-1 675 4G/5G polymorphisms and homocysteine levels with cardiovascular risk factors in a group of young patients with CVST. Eighty patients with CVST and an equal number of age and sex matched controls were enrolled. The protocol included demographic and clinical baseline characteristics, neuroimagistic aspects, genetic testing (PAI-1 675 4G/5G polymorphisms), biochemical evaluation (homocysteine—tHcy, the lipid profile, blood glucose, glycohemoglobin—HbA1c, high-sensitive C-reactive protein—hsCRP) data, therapy and prognosis. The PAI-1 675 4G/5G gene polymorphisms were significantly correlated with increased homocysteine level (tHcy) (p < 0.05), higher total cholesterol (TC) (p < 0.05), low- density lipoprotein cholesterol (LDLc) (p = 0.05) and high- sensitive C- reactive protein (hsCRP) (p < 0.05) in patients with CVST when compared with controls. From the PAI-1 gene polymorphisms, the PAI-1 675 4G/5G genotype presented statistically significant values regarding the comparisons of the blood lipids values between the CVST group and control group. The homocysteine (tHcy) was increased in both groups, patients versus controls, in cases with the homozygous variant 4G/4G but the level was much higher in the group with CVST (50.56 µmol/L vs. 20.22 µmol/L; p = 0.03). The most common clinical presentation was headache (91.25%), followed by seizures (43.75%) and focal motor deficits (37.5%). The superior sagittal sinus (SSS) was the most commonly involved dural sinus (56.25%), followed by the lateral sinus (LS) (28.75%). Intima—media thickness (IMT) values were higher in the patients’ group with CVST (0.95 mm vs. 0.88 mm; p < 0.05). The fatal outcome occurred 2.5% of the time. PAI-1 675 4G/5G gene polymorphisms and higher homocysteine concentrations were found to be significantly associated with CVST in young patients.

PAI-1 and tPA gene polymorphisms and susceptibility to chronic obstructive pulmonary disease in a sample of Turkish population.

The aim of this study was to assess the influence of plasminogen activator inhibitor-1 (PAI-1) 4G/5G or tissue plasminogen activator (tPA) I/D polymorphisms in chronic obstructive pulmonary disease (COPD) cases in a sample of Turkish population. PAI-1 4G/5G and tPA Alu-repeat I/D genetic polymorphisms in 153 COPD subjects and 160 controls were investigated using PCR-RFLP and PCR methods, respectively. 4G allele frequency was 0.62 and 0.39 for COPD and control groups, respectively. 4G allele had an estimated 2.56- fold [95% CI = 1.85-3.53] increased risk of COPD. tPA I allele frequency was 0.55 and 0.50, for COPD and control groups, respectively. I allele had an estimated 1.19-fold [95% CI = 0.87-1.62] increased risk of COPD. PAI-1 4G/4G and 4G/5G genotypes seemed to play a key role in the pathophysiology of COPD in Turkish individuals.

PAI-1 and tPA gene polymorphisms and susceptibility to chronic obstructive pulmonary disease in a sample of Turkish population

Abstract&#x0D; Objective: The aim of this study was to assess the influence of plasminogen activator inhibitor-1 (PAI-1) 4G/5G or tissue plasminogen activator (tPA) I/D polymorphisms in chronic obstructive pulmonary disease (COPD) cases in a sample of Turkish population.&#x0D; Methods: PAI-1 4G/5G and tPA Alu-repeat I/D genetic polymorphisms in 153 COPD subjects and 160 controls were investigated using PCR-RFLP and PCR methods, respectively.&#x0D; Results: 4G allele frequency was 0.62 and 0.39 for COPD and control groups, respectively. 4G allele had an estimated 2.56-fold [95% CI = 1.85–3.53] increased risk of COPD. tPA I allele frequency was 0.55 and 0.50, for COPD and control groups, respectively. I allele had an estimated 1.19-fold [95% CI = 0.87–1.62] increased risk of COPD&#x0D; Conclusions: PAI-1 4G/4G and 4G/5G genotypes seemed to play a key role in the pathophysiology of COPD in Turkish individuals.&#x0D; Keywords: COPD; Genetic susceptibility; Polymorphisms; Tissue-type plasminogen activator (tPA); Plasminogen activator inhibitor-1 (PAI-1)

Association between the 4G/5G polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene and sudden sensorineural hearing loss in Caucasian population: a meta-analysis.

To clarify the association between the 4G/5G polymorphism of plasminogen activator inhibitor-1 (PAI-1) and sudden sensorineural hearing loss (SSNHL). A systematic literature search of related studies up to August 30, 2019 in the PubMed and Embase databases was performed, and the results were displayed by odds ratios (ORs), and their 95% confidence intervals (CIs) were assessed using the STATA12.0 software using an allele model and a recessive model. Three eligible studies covering 519 subjects (241 cases, 278 controls) were identified. No statistically significant association was detected between the 4G/5G polymorphism and SSNHL in any model (allele model: 5G vs. 4G, OR = 0.952, 95% CI = 0.765-1.185, P = 0.662; recessive model: 5G/5G vs. 4G/5G + 4G/4G, OR = 0.841, 95% CI = 0.415-1.704, P = 0.631). There is no statistically significant association between the 4G/5G polymorphism of PAI-1 gene and SSNHL in the Caucasian population, and well-designed studies covering more patients and institutions should be conducted.

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

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.

Correlation Between PAI-1 Gene 4G/5G Polymorphism and the Risk of Thrombosis in Ph Chromosome-Negative Myeloproliferative Neoplasms.

Thrombosis has been recognized as one of the most significant risk factors of high mortality and disability in patients with Philadelphia (Ph) chromosome negative myeloproliferative neoplasms (MPNs). However, the risk factors of thrombotic events in these patients have not been completely understood. In this study, the clinical data of 58 patients with Ph-MPNs were obtained and analyzed, including 34 cases of essential thrombocytopenia (ET), 23 thrombotic events happened in 21 (36%) patients, among which 60% (14 of 23) with cerebral infarction, 17% (4 of 23) with coronary heart disease and 23% (5 of 23) with venous thrombosis. There were no significant differences in age, sex, and blood cell count between polycythemia vera (PV) and ET patients who have experienced thrombotic events and those who have not. In ET patients, the incidence of thrombotic events in plasminogen activator inhibitor-1 (PAI-1) genotype 4G4G was significantly higher than that in genotype 4G5G and genotype 5G5G (P < .05). The incidence of thrombotic events in PV and ET patients with infection was higher than those without infection (P < .05). Using logistic regression analysis, we found that PAI-1 genotype 4G4G and infection were associated with thrombotic events (odds ratio 6.744, 95% CI: 1.195-38.056 and 15.641 95% CI: 3.327-73.522). The 4G/4G polymorphism of PAI-1 gene and infection are independent risk factors of thrombotic events in patients with Ph-MPNs. PAI-1 gene 4G4G and infection in ET and PV patients with Janus kinase 2 (JAK2) V617F mutation were shown to be high risk of thrombotic events. Therefore, clinical doctors should put more attention on PAI-1 genotype 4G4G and infection in JAK2 V617F mutated patients with Ph-MPNs to prevent the thrombosis.

Apolipoprotein E and plasminogen activator inhibitor 1 gene polymorphism in children with chronic renal insufficiency associated with cardiovascular disease

BackgroundCardiovascular disease (CVD) is considered a major cause of death in renal insufficiency (RI). Contributing genetic factors is a recent focus of research. This study aims to elucidate apolipoprotein E (APO-E) and plasminogen activator inhibitor 1 (PAI-1) gene polymorphisms in RI children associated with CVD.MethodsWe studied 50 cases with chronic kidney disease (CKD) associated with CVD, and 30 healthy controls. Study sample was grouped as one on conservative treatment, the second on hemodialysis and the third was posttransplant. PAI-1 and APO-E gene polymorphisms were investigated using allele-specific polymerase chain reaction (AS-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) respectively.Results4G4G and 4G5G were the most common PAI-1 polymorphism denoting high association of 4 G allele in renal insufficiency associated with CVD with absent link to dyslipidemia, echocardiography changes or thrombosis. E3E3 was the most common among APO-E polymorphism without relation to dyslipidemia or thrombosis. Dyslipidemia was significantly linked to thrombosis. The study confirmed the role of dyslipidemia and hemodialysis in promoting thrombosis.ConclusionAlthough PAI 4G Genotyping did not show significant association with echocardiography severity or thrombotic severity, yet genetic expression for high levels of PAI in plasma is expected in response to CRI factors known to trigger its release, in addition to those related to dialysis. APO-E3E3 genotyping showed a significant association with echocardiography severity as it enhances APO-A which contributes to CVD. The current study confirmed a significant association between dyslipidemia and CVD; however, the prevalent patterns 4G and E3E3 did not show a significant association with dyslipidemia. The genetic role for APO-A, B, O, or even other isomers for APO-E should be further studied as well.

Plasminogen activator inhibitor-1 gene polymorphism as a risk factor for vascular complications in type 2 diabetes mellitus

BackgroundDiabetes mellitus (DM) can lead to microvascular and macrovascular damages through hyperglycemia that is the main cause of diabetic complications. Other factors such as hypertension, obesity, and hyperlipidemia may worsen or accelerate the others. Several studies have revealed definitive genetic predispositions to the development of type 2 diabetes mellitus (T2DM) and development of vascular complications. This study aimed to address the association between plasminogen activator inhibitor-1 (PAI-1) gene polymorphism and T2DM, and if this gene polymorphism may have a possible role in the development of vascular complications in T2DM. This study is a case control; it included 200 patients with T2DM, 117 patients had no vascular complications, and 83 had previous vascular complications (VCs). One hundred eighty volunteer blood donors were selected as a healthy control group. All patients and controls were subjected to clinical examination, and laboratory investigations included lipid profile, fasting and 2 h blood glucose, complete blood cell count, d-dimer, PAI-1, thrombin activatable fibrinolysis inhibitor (TAFI), and detection of PAI-1 gene polymorphism by real-time polymerase chain reaction (PCR).ResultsThe most prevalent genotype of PAI-1 gene polymorphism in all studied groups, including controls, was 4G/5G with the highest allele frequency as 4G. The 4G/5G and 4G/4G genotypes were associated with increased risk of DM development as compared to 5G/5G genotype. The 4G/5G and 4G/4G genotypes also had a highly significant increased risk of VCs among diabetic patients, as compared to 5G/5G. The 4G allele also was highly associated with DM with VCs. The d-dimer TAFI, PAI-1 showed the highest levels in 4G/5G genotype followed by 4G/4G genotype. The lowest level was expressed in 5G/5G genotype in diabetic patients with and without VCs. The univariable analysis showed that genotypes 4G/5G and 4G/4G were potentially risk factors for development of VCs with T2DM patients.ConclusionThis study concludes that the PAI-1 4G/5G polymorphism may be associated with T2DM and may be considered as a risk factor for development of thrombotic events. It may also help in selection and dosing of patients being treated with anticoagulant and fibrinolytic agents. Further large-scale studies are recommended to assess the possible role of environmental factors and gene interactions in the development of T2DM vascular risks.

Plasminogen activator inhibitor-1 gene polymorphisms in systemic lupus erythematosus: is there a risk for lupus nephritis among Egyptians?

Background Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by immune complexes formation and body organs damage. Recently, plasminogen activator inhibitor-1 (PAI-1) has been proposed recently to modulate the immune response. Aim of the study To elucidate whether there is possible role of two genetic polymorphisms in the PAI-1 gene: −675 4G/5G and HindIII C>G in lupus nephritis (LN) disease in Egyptian patients. Patients and methods Using PCR-restriction fragment length polymorphism, we genotyped 170 Egyptian patients with SLE; 80 fulfill the American College of Rheumatology criteria of LN and 90 SLE patients without LN for two polymorphisms of PAI-1 gene: −675 4G/5G and HindIII C>G. Results The 4G4G genotype, 4G allele of PAI 4G/5G polymorphism, and the G allele of the PAI-1 HindIII C>G polymorphism, all exhibited significant risks for proliferative LN [odds ratio (OR)=2.55; 95% confidence interval (CI): 1.02–21.11; P=0.022); (OR=2.43; 95% CI: 1.18–5.01; P=0.015); (OR=2.37; 95% CI: 1.01–5.58; P=0.045), respectively]. Moreover, PAI-1 4G/5G polymorphism was related to the chronicity index for LN (P G polymorphism was associated with the activity (P=0.016) and the chronicity (P Conclusion Egyptian patients with SLE with a polymorphism for −675 4G/5G and HindIII C>G of PAI-1 gene might have a higher susceptibility for the development of proliferative LN.

&amp;minus;675 4G/5G and &amp;minus;844 G/A of Plasminogne Activator Inhibitor-1 (Pai-1) Gene Polymorphisms and Type 2 Diabetes Mellitus in Tunisia: Case-Control Study

Background: The plasminogen activator inhibitor-1 (PAI-1) is a puissant antifibrinolytic factor; plasma PAI-1 level is high in type 2 diabetes. 4G/5G polymorphism of PAI-1 gene is a major genetic determinant of plasma PAI-1 levels, with 4G carriers having high PAI-1 level than 5G, theses pose the question about relation T2 patients and those polymorphisms. The aim of this study was to determine the relationship between the polymorphisms −675 4G/5G and −844 G/A of PAI-1 gene and type 2 diabetes mellitus. Methods: A case control study of 491 diabetic and 400 healthy controls. Genotyping of the polymorphism −675 4G/5G was done by PCR-ASA (polymerase chain reaction, allele specific amplification), and the polymorphism −844 G/A was done with PCR-RFLP (restriction fragment length polymorphism), the allelic frequency is calculated with hardy-Weinberg law, the statistic analysis was done by SPSS version 10. Results: Higher frequencies of The genotypes 4G/4G (p = 0.01) and 4G/5G of polymorphism −675 4G/5G were seen in diabetic (p = 0.05) and higher frequencies of 5G/5G was seen in controls (p −844 G/A was seen in diabetics and G/G was seen in controls (p = 0.01). Conclusion: Our study found association between 4G allele of −675 4G/5G and A allele of −844 G/A of PAI-1 gene and having type 2 diabetes mellitus in Tunisian population.

Association of TAFI gene polymorphisms with severity of coronary stenosis in stable coronary artery disease

IntroductionCoronary stenosis is a consequence of atherosclerotic plaque progression that is associated with impaired fibrinolysis. Thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor 1 (PAI-1) are fibrinolysis inhibitors whose levels are influenced by acquired conditions and by polymorphisms. This study therefore aimed to investigate the association of TAFI and PAI-1 gene polymorphisms with severity of coronary stenosis in subjects with stable coronary artery disease (CAD). Materials and methodsA total of 327 subjects suspected with CAD who underwent a coronary angiogram were recruited. Gensini score was applied to stratify the severity of coronary stenosis. Based on the Gensini score, the subjects were categorized into low-medium (<20) or high (≥20) groups. The study polymorphisms included TAFI Ala147Thr (505G/A), Thr325Ile (1040C/T), +1542C/G, +1583T/A and PAI-1 -675 4G/5G. Most polymorphisms were genotyped by allele-specific polymerase chain reaction, except for TAFI Thr325Ile that was genotyped by polymerase chain reaction-restriction fragment length polymorphism. ResultsA significant increase in the Gensini score was found in TAFI 505A and +1583A allele carriers. Binary regression analysis revealed the independent association of the TAFI 505G/A and +1583T/A polymorphisms with a high Gensini score [adjusted OR = 1.67 (95% CI: 1.03, 2.73) and 1.69 (95% CI: 1.04, 2.76), respectively]. Neither the homozygous PAI-1 -675 4G/4G nor the heterozygous 4G/5G was associated with a high Gensini score. ConclusionsThe results indicated the contribution of TAFI polymorphisms to atherosclerosis progression and severity of coronary stenosis in stable CAD.

The roles of PAI-1 gene polymorphisms in atherosclerotic diseases: A systematic review and meta-analysis involving 149,908 subjects

BackgroundThe roles of plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms in atherosclerotic diseases were intensively analyzed, but the results of these studies were inconsistent. Therefore, we performed this study to better assess the relationship between PAI-1 genetic variations and atherosclerosis. MethodsEligible studies were searched in PubMed, Medline, Embase and Web of Science. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess relationship between PAI-1 polymorphisms and atherosclerotic diseases. ResultsNinety-nine studies involving 62,739 cases and 87,169 controls were finally included. Significant associations with the risk of atherosclerosis were detected for the rs2227631 polymorphism in the dominant model (95% CI 0.84–1.00), for the rs1799889 polymorphism in the dominant (95% CI 1.01–1.18), recessive (95% CI 0.90–0.98) and allele (95% CI 1.01–1.12) models. Further subgroup analyses based on type of disease and ethnicity of participants suggested that the rs2227631 polymorphism was significantly associated with the risk of coronary artery disease in the dominant (95% CI 0.71–0.94) and allele (95% CI 0.80–0.94) models, whereas the rs1799889 polymorphism was significantly associated with the risk of myocardial infarction (dominant model: 95% CI 1.09–1.57; recessive model: 95% CI 0.71–0.96; allele model: 95% CI 1.05–1.28) and cerebral infarction (dominant model: 95% CI 1.68–3.51; additive model: 95% CI 0.39–0.77; allele model: 95% CI 1.23–2.00). Moreover, the rs1799889 polymorphism was also significantly correlated with the risk of atherosclerosis in both Asians (dominant model: 95% CI 1.10–1.83; allele model: 95% CI 1.03–1.41) and Caucasians (recessive model: 95% CI 0.87–0.97; allele model: 95% CI 1.01–1.12). ConclusionIn conclusion, our findings indicate that PAI-1 rs2227631 and rs1799889 polymorphisms may serve as genetic biomarkers of atherosclerotic diseases.

Plasminogen activator inhibitor-1 polymorphisms as a risk factor for chronic periodontitis in North Indian population

ObjectivesImpaired plasminogen activator inhibitor-1 (PAI-1), controlling coagulation and the fibrinolytic system is supposed to be involved in the pathogenesis of periodontitis. This study was performed to examine the association of PAI-1 gene polymorphisms with Chronic Periodontitis (CP) and alveolar bone loss severity involved with the disease and for understanding the role of genetic contributions in disease progression. Methods87 volunteers were included in the study. Genomic DNA was isolated from peripheral blood, subsequently, DNA samples were subjected to polymerase chain reaction and endonuclease digestion. Direct gene sequencing were performed for all the samples to identify genotype polymorphisms (rs 11560324) in the 3’ untranslated region of PAI-1 gene. For bone loss assessment full mouth IOPA was taken. ResultsStatistical analysis showed that for SNP PAI-I in 3’ UTR, genotype CC (homozygous mutant) and allele C (mutant) has a risk associated with CP, although statistically significant association was not found. An increased risk of association of disease severity with CG (heterozygous mutant) and CC (homozygous mutant) genotypes, i.e., an increased carriage rate of genotype CG and CC (homozygous mutant) was evident with the increase in the severity of CP, highlighting an increased susceptibility to CP due to this gene polymorphisms. ConclusionPAI-1 genotype has a risk association with CP and alveolar bone loss severity in North-Indian population.

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

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 &gt; A, −6754G/5G, +43G &gt; A, +9785G &gt; A and +11053T &gt; 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 &lt; 0.0001, odds ratio (OR) = 3.18; 5G: P &lt; 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.

The Role of Pai-1 Gene 4g/5g Polymorphism and Diagnostic Value of Biomarkers in Allergic and Non-Allergic Asthma Phenotype.

SUMMARY – Asthma is a chronic inflammatory disease that is characterized by reversible obstruction of airways, bronchial hyper-reactivity and airway remodeling. The etiology of asthma is multifactorial, with inheritance playing an important role. The aim of our study was to investigate the importance of biomarkers of asthma and the role of plasminogen activator inhibitor-1 (PAI-1) gene as a genetic factor that could be involved in the pathogenesis of asthma. The research was conducted at Jordanovac University Department for Lung Diseases and Croatian Institute of Transfusion Medicine. The research included 149 patients with asthma and 89 healthy individuals. We collected demographic data of both study groups, determined asthma severity using GINA guidelines, and the values of biomarkers and PAI-1 by using laboratory techniques. Based on the results, we concluded that patients with allergic phenotype of asthma were younger, had better lung function and higher levels of IgE. By observing FeNO values, we were not able to distinguish asthmatic patients that had been diagnosed with obstruction of airways from asthmatic patients with normal lung function because FeNO indicates the inflammatory component of disease. The 4G/5G polymorphism of PAI-1 gene did not show any statistically significant difference in the distribution of 4G/4G, 4G/5G and 5G/5G between the group of asthmatic patients and control group.

Association of Plasminogen Activator Inhibitor-1 Gene Polymorphisms and Methylene Tetrahydrofolate Reductase Polymorphisms with Spontaneous Miscarriages

Aim: The objective of this study was to investigate a possible correlation between the plasminogen activator inhibitor-1 (PAI-1) and methylene tetrahydrofolate reductase (MTHFR) polymorphisms and unexplained spontaneous miscarriages (SM). Materials and Methods: PAI-1 polymorphisms were evaluated in 150 women with pregnancy in their history. One hundred women with a history of SM formed the study group and 50 women with normal pregnancies served as the control group. Also, the combination of PAI-1 and MTHFR polymorphisms were evaluated in 138 women out of a total of 150, which included 92 women with SM in their history compared to 46 women in the control group. For statistical analysis, χ² test, Phi, and Cramer V tests were used; p < 0.05 was taken as a statistically significant result. Results: Our findings show: (a) the correlation between SM and PAI-1 mutations reaches statistical significance (p = 0.026); (b) there was a statistically significant difference between heterozygous PAI-1 in women with only 1 SM compared to the control group (p = 0.047); (c) the comparison of combinations of both mutations, PAI-1 and MTHFR, with the control group demonstrates statistical significance in favor of women with SM and both mutations (p = 0.022). Conclusion: PAI-1 and MTHFR polymorphisms may play an important role in pregnancy complications because heterozygous PAI-1 mutations and a combination of both PAI-1 and MTHFR mutations might contribute to SM.

Evaluating the Prevalence of Plasminogen Activator Inhibitor-1 Gene Polymorphism in Patients with Thyroid Tumors from North West of Iran

Evaluating the Prevalence of Plasminogen Activator Inhibitor-1 Gene Polymorphism in Patients with Thyroid Tumors from North West of Iran