Plasminogen activator inhibitor-1 (PAI-1) 4 G/5 G polymorphism and endometrial cancer. Influence of PAI-1 polymorphism on tissue PAI-1 antigen and mRNA expression and tumor severity

Plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism may have significance for PAI-1 expression. High levels of PAI-1 in endometrial cancer patients are associated with a poor prognosis. The objective of this study was to evaluate the PAI-1 4G/5G polymorphism in women with and without endometrial cancer and to analyze the influence of this polymorphism on PAI-1 expression in endometrial tissue.In 423 women (212 patients with endometrial cancer and 211 controls) PAI-1 4G/5G polymorphism was determined by PCR amplification using allele-specific primers. Quantitative real-time RT-PCR assay was used to quantify PAI-1 mRNA and PAI-1 protein levels were quantified by ELISA in tissue extracts from 33 patients with endometrial cancer and from 70 endometrial tissues from control women. The frequency of PAI-1 4G/4G genotype (P = 0.010) and the PAI-1 4G allele (P = 0.009) was significantly higher in patients than in controls. The frequency of PAI-1 4G allele was significantly higher in patients with stage IB than in those with stage IA (P = 0.03). Control women with the 4G/4G genotype had higher endometrial PAI-1 protein (P = 0.018) and mRNA (P = 0.004) levels than those with the 5G/5G genotype. A significant increase in PAI-1 protein and mRNA was observed in endometrial cancer tissue in comparison with the endometrial tissue from control women (P < 0.01). In conclusion, frequencies of the PAI-1 4G allele and 4G/4G genotype were found significantly more often in women with endometrial cancer than in controls. PAI-1 levels in endometrial tissue seem to be associated with PAI-1 4G/5G polymorphism. These findings suggest that the PAI-1 4G/4G genotype may be associated with the risk of endometrial cancer in a Caucasian population. Further studies with a larger number of patients are needed to clarify the influence of this PAI-1 polymorphism in endometrial cancer.     

The effect of the plasminogen activator inhibitor-1 4G/5G polymorphism on the thrombotic risk

Plasminogen activator inhibitor (PAI-1), is the central component of the fibrinolytic system. A deletion/insertion (4G/5G) polymorphism in the promoter region of the PAI-1 gene has been correlated with levels of plasma PAI-1. The 4G allele is associated with higher levels of PAI-1, and might increase the risk for intravascular thrombosis. However, the contribution of this genetic variant to the risk for thrombosis, both arterial and venous, has not been clearly established. A broad spectrum of findings regarding the effect of the 4G allele on thrombotic risk in different target organs has been reported. Our aim is to summarize the variable influence of this polymorphism on thrombotic events in different tissues or organs and explain the underlying mechanisms accounting for these differences.     

Plasminogen activator inhibitor 1 expression in platelets is not influenced by the 4G/5G promoter polymorphism

In the present study we investigated the influence of the 4G/5G promoter polymorphism of the PAI-1 gene on the levels of PAI-1 mRNA and protein in platelets. After a screening of healthy male subjects, thirty-eight subjects homozygote for either the 4G or 5G allele were investigated. mRNA levels were quantified by real-time PCR and PAI-1 antigen in platelets and plasma was analysed by ELISA. The platelet PAI-1 mRNA levels correlated significantly with the PAI-1 antigen content, but there was no association between the polymorphism and mRNA levels, or protein levels in platelets. Also, plasma levels of PAI-1 antigen were not associated with homozygosity of the 4G/5G polymorphism, but as expected BMI and triglycerides emerged as significant predictors of plasma PAI-1 levels. The importance of the 4G/5G polymorphism on PAI-1 levels is controversial and the present study shows that although levels of platelet mRNA are related to its content of PAI-1 protein, there is no association between the 4G/5G promoter polymorphism and platelet PAI-1 mRNA or protein expression.     

Plasminogen activator inhibitor-1 4G/5G polymorphism in breast cancer patients and its association with tissue PAI-1 levels and tumor severity

BACKGROUND: The plasminogen activator inhibitor type 1 (PAI-1) 4G/5G polymorphism may have significance for PAI-1 expression. High levels of PAI-1 in breast cancer patients are associated with a poor prognosis. In this study, we analyzed the influence of the PAI-1 4G/5G polymorphism on tissue PAI-1 levels and its association with tumor severity in women with breast cancer. MATERIAL AND METHODS: We studied 104 women with breast carcinoma (patient group) and 104 healthy age-matched women (control group). In patients and controls, the PAI-1 4G/5G polymorphism was determined by PCR amplification using allele-specific primers. In patients, PAI-1 levels were quantified in breast cancer tissue by using an ELISA. RESULTS: The frequency of the PAI-1 4G allele tended to be higher in patients than in controls (p=0.062). The presence of the 4G allele (4G/5G plus 4G/4G genotypes) was significantly higher among patients with histological grade 3 tumors than among those with grade 1 tumors (p=0.026). Furthermore, patients with the 4G/4G genotype had significantly higher tissue PAI-1 levels than those with the 5G/5G genotype. Moreover, tissue PAI-1 antigen levels were significantly and positively correlated with tumor severity (p=0.003) and tumor size (p=0.009). However, no significant differences in PAI-1 level were observed in relation to menopause, hormone receptor or nodal status. CONCLUSION: Tissue PAI-1 antigen levels and tumor severity seem to be associated with the PAI-1 4G/5G polymorphism. Further studies with a larger number of patients are needed to clarify the influence of this polymorphism in breast cancer.     

The impact of the PAI-1 4G/5G polymorphism on the outcome of patients with ALI/ARDS

Intoduction

Increased levels of plasminogen activator inhibitor-1 (PAI-1) have been associated with worse outcome in ALI/ARDS. A single guanosine insertion/deletion (4G/5G) polymorphism in the promoter region of the PAI-1 gene, may play an important role in the regulation of PAI-1 expression. The objective of the study was to evaluate the effect of this polymorphism on the outcome of critically ill patients with ALI/ARDS.

Materials and Methods

52 consecutive ventilated patients with ALI/ARDS were studied. Bronchoalveolar lavage was performed within 48 hours from diagnosis. Measurement of plasma and BALF PAI-1 activity and D-dimers levels, and 4G/5G genotyping of PAI-1 were carried out. The primary outcome was 28-day mortality, and secondary outcomes included organ dysfunction and ventilator-free days.

Results

17 patients were homozygotes for the 4G allele. Severity scores were not different between subgroups upon study enrollment. 28-day mortality was 70.6% and 42.9% for the 4G-4G and the non-4G-4G patients, respectively (p = 0.06). PAI-1 activity levels and D-dimer in plasma and BALF were not significantly different between the 4G-4G and the non-4G-4G subgroups. In the multivariate analysis, genotype 4G/4G was the only variable independently associated with 28-day mortality (Odds Ratio = 9.95, 95% CI: 1.79-55.28, p = 0.009). Furthermore, genotype 4G/4G and plasma PAI-1 activity levels were independently negatively associated with ventilator free days (p = 0.033 and p = 0.008, respectively).

Conclusions

ALI/ARDS patients, homozygous for the 4G allele of the PAI-1 gene, experienced higher 28-day mortality. This genotype was associated with a reduction in the number of days of unassisted ventilation and was inversely associated with the number of days without organ failure.     

Association of plasminogen activator inhibitor-1 4G/5G promoter polymorphism with recurrent cerebral infarction in China’s North Jiangsu Province

BACKGROUND:Many international studies have shown that plasminogen activator inhibitor-l(PAI-1)4G/5G promoter polymorphism does not increase the risk for cerebral infarction.OBJECTIVE:Using PCR methodology and agarose electrophoresis to detect PAl-1 4G/5G promoter polymorphism in patients with recurrent cerebral infarction in the North Jiangsu Province of China,and to compare results with healthy subjects and patients with first-occurrence cerebral infarction in the same region.DESIGN,TIME AND SETTING:Non-randomized,concurrent,control trial.A total of 122 cerebral infarction patients were admitted to Xuzhou Medical College Hospital's Department of Neurology and Xuzhou Central Hospital's Department of Neurology between July 2003 and August 2006.PARTlCIPANTS:The patients consisted of 63 males and 59 females,aged(62±10)years.They were divided into first-occurrence(n=58)and recurrence(n=64)groups.In addition,50 healthy subjects that underwent physical examination in the outpatient department,including 26 males and 24 females,aged (60±12)years,were selected as controls.METHODS AND MAIN OUTCOME MEASURES:PAI-1 4G/5G pmmoter polymorphism was detected and analyzed using PCR methodology and agarose electrophoresis.RESULTS:Significant differences were determined in terms of genotypic frequency and allele frequency of PAI-1 4G/5G promoter polymorphism,in patients with first-occurrence or recurrent cerebral infarction,when compared with healthy subjects(P<0.05).There was,however,no significant differenco between the first-occurrence and recurrence groups(P>0.05).CONCLUSION:PAI=1 4G/5G promoter polymorphism is genetic risk factor for cerebral infarction in China.However,it may be associated with recurrence of cerebral infarction in padents from the North Jiangsu Province of China.     

PAI—1启动子区4G／5G基因多态性与脑卒中的相关研究

目的 探讨纤溶酶原激活物抑制物－1（PAI－1）启动子区基因多态性与脑卒中的关系。方法 通过 多聚酶链反应（PCR）技术和发色底物法（RLISA）,测定96例脑卒中患者和60名健康对照者的白细胞PAI－1启动子区4G／5G多态性位点的基因型及血浆PAI－1活性。结果 脑梗死（CI）组血浆PAI－1活性明显高于脑出血（CH）组及对照组,CI和CH组中均以纯合子4G／4G基因型患者的PAI－1血浆活性水平为最高,5G／5G基因型最低,杂合子4G／5G基因型居中;4G纯合子基因型与其它二型 之间比较差异均有显著意义,4G／5G与5G／5G基因型之间比较无显著意义。CI组4G／4G纯合子基因型与对照组比较有显著性差异（均P＜0．05）,CI组基因型与CH组及CH组与对照组基因型比较均无统计学意义（P＞0．05）。CI组女性4G纯合子基因型患者血浆PAI－1活性与同型男性患者比较有显著性差异（P＜0．05）。结论 纯合子4G／4G基因型可能是CI发病的危险因素之一,4G纯合子个体可能具有较高的CI发病倾向,尤其可能与女性CI发病相关。     

Association between PAI-1 4G/5G Polymorphisms and osteonecrosis of femoral head: A Meta-analysis

Background

The polymorphism of the plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene has been correlated with susceptibility to osteonecrosis of the femoral head (ONFH), but study results are controversial. The aim of this study was to derive a more precise estimation of the relationship between the PAI-1 4G/5G Gene polymorphism and ONFH by performing a meta-analysis.

Methods

The meta-analysis was based on five eligible case-control studies involving 419 cases and 969 controls and summarized data indicating the association between PAI-1 polymorphism and risk of osteonecrosis of the femoral head. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to assess the strength of this association in the random-effects model or fixed-effects model.

Results

A significant association between PAI-1 4G/5G polymorphism and ONFH susceptibility was observed for 4G4G + 4G5G vs. 5G5G (OR = 1.766, 95% CI 1.279–2.437, P = 0.001), 4G/4G vs. 4G/5G + 5G/5G (OR = 2.050, 95% CI 1.581–2.657, P = 0.000), 4G/4G vs. 5G/5G (OR = 2.553, 95% CI 1.345–4.846, P = 0.004), and 4G vs. 5G (OR = 1.758, 95% CI 1.236–2.500, P = 0.002). No significant association between PAI-1 4G/5G polymorphism and ONFH susceptibility was observed for 4G/5G vs. 5G/5G (OR = 1.327, 95% CI 0.939–1.877, P = 0.109).

Conclusions

This meta-analysis suggested that 4G/5G polymorphism of the PAI-1 gene was a risk factor for ONFH. This study also suggests that the PAI-1 4G4G genotype may indicate a risk for ONFH.     

Association of plasminogen activator inhibitor-1 4G/5G promoter polymorphism with recurrent cerebral infarction in China’s North Jiangsu Province*☆

BACKGROUND： Many international studies have shown that plasminogen activator inhibitor-1 （PAl-l） 4G/5G promoter polymorphism does not increase the risk for cerebral infarction.
OBJECTIVE： Using PCR methodology and agarose electrophoresis to detect PAI-1 4G/5G promoter polymorphism in patients with recurrent cerebral infarction in the North Jiangsu Province of China, and to compare results with healthy subjects and patients with first-occurrence cerebral infarction in the same region.
DESIGN, TIME AND SETTING： Non-randomized, concurrent, control trial. A total of 122 cerebral infarction patients were admitted to Xuzhou Medical College Hospital＇s Department of Neurology and Xuzhou Central Hospital＇s Department of Neurology between July 2003 and August 2006.
PARTICIPANTS： The patients consisted of 63 males and 59 females, aged （62 ± 10） years. They were divided into first-occurrence （n = 58） and recurrence （n = 64） groups. In addition, 50 healthy subjects that underwent physical examination in the outpatient department, including 26 males and 24 females, aged （60 ±12） years, were selected as controls.
METHODS AND MAIN OUTCOME MEASURES： PAl-1 4G/5G promoter polymorphism was detected and analyzed using PCR methodology and agarose electrophoresis.
RESULTS： Significant differences were determined in terms of genotypic frequency and allele frequency of PAI-1 4G/5G promoter polymorphism, in patients with first-occurrence or recurrent cerebral infarction, when compared with healthy subjects （P 〈 0.05）. There was, however, no significant difference between the first-occurrence and recurrence groups （P 〉 0.05）.
CONCLUSION： PAl- 1 4G/5G promoter polymorphism is genetic risk factor for cerebral infarction in China. However, it may be associated with recurrence of cerebral infarction in patients from the North Jiangsu Province of China.     

PAI-1基因启动区4G/5G多态性与2型糖尿病并发脑梗死的关系

目的研究PAI-1基因启动区4G/5G多态性在中国北方汉族人2型糖尿病(DM)患者及并发脑梗死(CI)患者中的分布,以及各组中血浆PAI-1抗原水平的变化。方法将280名受试对象分为4组:健康对照组(92例)、非DM脑梗死组(60例)、单纯DM组(88例)及DM并发CI组(40例)。全部受试对象均需应用ELISA法测定血浆PAI-1抗原水平,等位基因特异性引物PCR扩增技术测PAI-1基因启动区4G/5G多态性。结果DM、CI患者血浆PAI-1抗原水平显著升高,中国北方汉族人中,DM组中脑梗死患者5G等位基因频率和5G/5G基因型频率不仅显著高于健康对照组,也显著高于DM无脑梗死组和无DM脑梗死组。在DM组中,5G纯合子携带者发生CI的风险增加3.81倍,有统计学意义。结论PAI-1启动区5G/5G基因型是2型DM患者中CI高发的易感基因型之一。     

HMG CoA reductase inhibitor suppresses the expression of tissue factor and plasminogen activator inhibitor-1 induced by angiotensin II in cultured rat aortic endothelial cells

BACKGROUND: It has been demonstrated that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (HRIs) reduce the incidence of acute cardiovascular events in patients with hyperlipidemia. Recent reports have shown that the protective effects of these drugs against cardiovascular events are also observed in patients without hyperlipidemia, but the mechanism of this favorable effect still remains unclear. In this study, the effects of HRIs on the endothelial regulation of thrombus formation were elucidated. METHODS AND RESULTS: The mRNA and protein expression of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) induced by angiotensin II (Ang II) were evaluated in cultured rat aortic endothelial cells. Pretreatment with simvastatin (0.03-3 microg/ml) significantly inhibited TF and PAI-1 induction by Ang II in a dose- and time-dependent manner. These inhibitions were significantly attenuated by mevalonic acid or geranylgeranyl pyrophosphate. Both Rho inhibitor, C3 exoenzyme, and Rho kinase inhibitor, Y-27632, mimicked the inhibitory effects of simvastatin against TF and PAI-1 induced by Ang II. This result suggested that the Rho/Rho kinase pathway is related to the TF and PAI-1 induction by Ang II. CONCLUSION: It was indicated that simvastatin maintains endothelial cells to be antithrombotic by inhibiting TF and PAI-1 expression via the Rho/Rho kinase pathways in which AngII induces TF and PAI-1 expression. These observations explain, at least partly, the mechanism of the favorable effects of simvastatin in reducing the thrombotic events.     

Residual vein thrombosis and onset of post-thrombotic syndrome: Influence of the 4G/5G polymorphism of plasminogen activator inhibitor-1 gene

Background

Plasminogen activator inhibitor-1 (PAI-1) is the most important inhibitor of plasminogen activator. The functional 4G/5G polymorphism of the gene coding for PAI-1 may affect PAI-1 plasmatic activity, influencing the imbalance between coagulation and fibrinolysis cascades.In this prospective cohort analytic study, we investigated the role of this single nucleotide polymorphism in the persistence of thrombotic lesion and the occurrence of post-thrombotic syndrome.

Patients/Methods

In a group of 168 patients with post-surgical deep vein thrombosis of the legs, we analyzed the 4G/5G polymorphism in the promoter of PAI-1 gene and plasmatic PAI-1 activity.Enrolled patients were divided in two groups: patients with 4G/5G polymorphism and increased PAI-1 activity (n = 85) and patients without 4G/5G polymorphism and normal PAI-1 activity (n = 83). All patients were treated according to current protocols and re-examined after 3, 12 and 36 months in order to evaluate the persistence of thrombotic lesion and the occurrence of post-thrombotic syndrome.

Results

We found a significantly increased PAI activity in carrier of the 4G allele, who experienced much more frequently a persistence of thrombosis after 3, 12 and 36 months and/or the development of post-thrombosis syndrome, in spite of the anticoagulant treatment.

Conclusions

These data not only confirm the role played by PAI-1 activity and by the 4G/5G SNP of the PAI-1 gene, but also suggest that current therapeutic protocols, recommending the administration of low weight molecular heparin and oral anticoagulant for the treatment of deep vein thrombosis, could be non sufficient for patients genetically predisposed to a less efficient clot lysis.     

血浆中PAI-1和TAFI水平与溶栓后出血性转化相关性研究

目的探索PAI及TAFI对急性脑梗死静脉溶栓后出血性转化的预警作用。方法前瞻性的将溶栓患者分为出血转化组和无出血转化组,对两组患者溶栓前及溶栓后静脉血浆PAI及TAFI浓度进行对比及统计学分析。结果溶栓前两组基线PAI-1水平差异有明显统计学意义(P=0.037)。溶栓后次日复查晨血PAI-1水平出血转化组明显较无出血转化组值更低(P=0.035)。溶栓前出血转化组的基线TAFI水平较无出血转化组比较TAFI值更低(P=0.024)。溶栓后次日复查晨血出血转化组TAFI值同样低于无出血转化组(P=0.042)。结论血浆中PAI-1和TAFI水平与溶栓后出血性转化相关性较高。当溶栓前及溶栓后PAI-1及TAFI的低水平表达均可增加溶栓后出血性转化的风险。     

Relationships between fibrinogen, plasminogen activator inhibitor-1, and their gene polymorphisms in current smokers with essential hypertension

Background: To elucidate the role of some haemostatic gene polymorphisms and environmental factors, we studied fibrinogen (Fb), plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (t-PA) levels with respect to Fb G455A and PAI-1 4G/5G gene polymorphisms in smokers and nonsmokers with essential hypertension. Material and methods: The study was done in 90 patients (including 30 smokers) with essential hypertension (HT) and 40 controls (including 8 smokers). Fb and PAI-1 genotypes were PCR identified. The groups did not differ significantly as to genotype frequencies. Results: When allele A455 carriers were compared, HT patients had significantly higher Fb (p=0.015) and t-PA levels (p=0.013). Comparison of 4G allele carriers (4G/4G homozygotes) revealed significantly higher Fb (p=0.045), PAI-1 (p=0.009), and t-PA levels (p=0.007) in HT patients than controls. Interactions of Fb and PAI-1 gene polymorphisms with smoking were disclosed in HT patients only. Allele A455-carrying HT smokers compared with nonsmokers had significantly higher t-PA (12.1±5.8 vs. 7.4±3.1 ng/ml; p=0.002) and tendency to higher Fb (3.36±0.74 vs. 2.95±0.70 g/l; p=0.075) levels. Higher Fb levels were disclosed in 4G/4G smokers than nonsmokers (3.31±0.81 vs. 2.84±0.85 g/l; p=0.064). Finally, in smokers, significantly higher levels of PAI-1 were found in 4G/4G (42.1±29.4 ng/ml) as compared with 4G/5G (18.6±13.7 ng/ml; p=0.025) and 5G/5G (14.4±10.8 ng/ml; p=0.044) genotypes. Conclusions: Smoking potentiates the prothrombotic effect of allele A455 and PAI-1 4G/4G genotype in untreated essential hypertension, reflected by increased levels of haemostatic risk factors and accelerated progression of cardiovascular diseases.     

Plasminogen activator inhibitor-1 levels in severe and morbid obesity. Effect of weight loss and influence of 4G/5G polymorphism

INTRODUCTION: An association between an increase in plasminogen activator inhibitor type 1 and obesity has been described. It has also been shown that a decrease in adiposity has beneficial effects. However, less information is available regarding morbid obesity and hypofibrinolysis. The aim of the present study was to evaluate the effect of weight loss and the influence of the plasminogen activator inhibitor type 1 promoter 4G/5G genotype on plasminogen activator inhibitor type 1 levels in severe and morbid obesity. MATERIALS AND METHODS: Sixty-seven obese patients were studied before and three months after a weight reduction program, and compared with 67 controls. We determined plasminogen activator inhibitor type 1 antigen and activity levels, tissue type plasminogen activator antigen levels, 4G/5G genotype and biochemical parameters in both groups. RESULTS: A significant increase in plasminogen activator inhibitor type 1 antigen and activity was observed in obese patients in comparison with the control group (P<0.001). No significant differences in plasminogen activator inhibitor type 1 levels among 4G/5G genotypes were obtained. After weight loss, a significant decrease in plasminogen activator inhibitor type 1 antigen and activity was observed (P<0.001). A significant and positive correlation was observed in percentage changes in plasminogen activator inhibitor type 1 and body mass index (P=0.02). CONCLUSIONS: A decrease in body mass index in severe and morbid obesity shows a favourable effect on the fibrinolytic system due to a decrease in plasminogen activator inhibitor type 1 levels. However, no influence of 4G/5G polymorphism has been observed in this setting.     

急性脑血管病患者血浆t-PA、PAI-1活性测定及意义

目的 研究急性脑血管病（脑梗死和脑出血）患者的血浆组织型纤溶酶原激活物（t-PA）和纤溶酶原激活物抑制物（PAI-1）的活性变化及临床意义.方法 采用酶联免疫吸附法测定67例急性脑梗死和53例脑出血患者的t-PA和PAI-1的活性,并计算P/t值,与50例正常对照组进行比较分析.结果 急性脑血管病组患者急性期（7d内）血浆t-PA及PAI-1活性均升高,与正常对照组比较有显著性差异（P＜0.05） 脑梗死组P/t值与正常对照组比较有显著性差异（P＜0.05） 脑出血组P/t值与正常对照组比较无显著性差异（P＞0.05）.结论 脑梗死和脑出血患者急性期血浆P/t改变不同 脑梗死患者急性期P/t降低,体内处于相对纤溶亢进状态 脑出血患者P/t变化不明显,体内凝血纤溶机制相对平衡P/t值可以更好地反映血液中的纤溶活性.     

纤溶酶原激活物抑制剂-1-675 4G/5G基因及纤维蛋白原β-148C/T基因多态性与脑梗死关系的研究

目的探讨纤溶酶原激活物抑制剂-1（PAI-1）-675 4G/5G及纤维蛋白原（Fg）β-148C/T基因多态性与脑梗死的关系。方法检测140例健康体检者（对照组）和220例脑梗死患者（CI组）PAI-1-675 4G/5G及Fgβ-148C/T基因多态性,并分析两组基因在正常人群及脑梗死患者中的频率分布特点。结果CI组Fgβ-148C/T位点T等位基因频率为0.33,对照组为0.225,两组比较差异具有统计学意义（P=0.0026）。CI组PAI-1-675 4G等位基因频率为0.48,对照组为0.56,两组比较差异具有统计学意义（P=0.037）,以5G/5G基因型作为参考,4G/4G基因型发生CI的OR值为0.52（95%CI：0.282～0.958,P=0.027）;携带CC和4G/4G基因型发生CI的OR值为0.48（95%CI：0.253～0.91,P=0.023）。结论本研究发现Fgβ-148T等位基因是CI发病的危险因素,4G/4G纯合子是CI的保护因素,CC基因型加强4G/4G基因型的CI保护作用。     

Regular exercise, plasminogen activator inhibitor-1 (PAI-1) activity and the 4G/5G promoter polymorphism in the PAI-1 gene.

The aim of this controlled randomised clinical trial was to investigate the effects of regular low to moderate intensity physical activity on plasminogen activator inhibitor-1 (PAI-1) activity during three years while taking into account the 4G/5G polymorphism in the promoter of the PAI-1 gene. Male subjects (age 52-62 years, n = 132) were randomised into an exercise or a (non-intervention) reference group. Aerobic threshold increased by 8.8% (p = 0.025) in the exercise group, and decreased by 1.1% in the non-intervention group, while PAI-1 activity did not change significantly in either study group. However, homozygotes for the 4G allele in the exercise group showed a 36% reduction in PAI-1 (p = 0.025). In conclusion, although regular moderate physical activity did not decrease PAI-I activity in the whole group, regular exercise may be effective for controlling elevated PAI-1 level in subjects homozygous for the 4G allele.