A Novel G/a and the 4g/5g Polymorphism Within the Promoter of the Plasminogen Activator Inhibitor-1 Gene in Patients With Deep Vein Thrombosis

Grubic, Nelly; Stegnar, Mojca; Peternel, Polona; Kaider, Alexandra; Binder, Bernd R.

doi:10.1016/s0049-3848(96)00211-3

Cited by 88 publications

(105 citation statements)

References 21 publications

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“…The two known promoter polymorphisms showed similar frequencies as previously reported in other Caucasian populations [24,26].…”

Section: Resultssupporting

confidence: 85%

“…The two other variants, both in the promoter, were the common single-base-pair guanine deletion/insertion, 4G/5G, at −675 [24,25] and the SNP −844 A>G [26]. The two known promoter polymorphisms showed similar frequencies as previously reported in other Caucasian populations [24,26].…”

Section: Resultssupporting

confidence: 75%

“…All the polymorphisms were in Hardy-Weinberg equilibrium (Table 1), except the −844 A>G variant which differed significantly (χ 2 =5.49, p=0.02), as was previously described [26].…”

Section: Resultssupporting

confidence: 75%

“…Importantly, the −675 4G/5G has been found to correlate with higher plasma PAI-1 activity in patients with myocardial infarction [24,25] and in subjects with deep vein thrombosis [26]. In contrast, another study failed to show any effect of the −844A>G SNP on plasma PAI-1 level [26].…”

Section: Discussionmentioning

confidence: 99%

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PAI-1 polymorphisms modulate phenotypes associated with the metabolic syndrome in obese and diabetic Caucasian population

et al. 2003

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Aim/hypothesis. Plasminogen activator inhibitor-1 (PAI-1) is a main regulator of the endogenous fibrinolytic system and modulates the thrombosis progression. We analyzed genetic contributions of PAI-1 mutations to the metabolic syndrome and to its complications. Methods. PAI-1 promoter and coding sequences were screened for mutations. Genotypes were determined for 1067 unrelated individuals of a French Caucasian cohort, selected for diabetes and obesity. Association between PAI-1 polymorphisms and phenotypes related to metabolic syndrome were statistically studied.Results. There were five variants identified: two common polymorphisms, −765 4G/5G and −844A>G, in the promoter, and three new non-synonymous SNPs, Ala15Thr, Val17Ile and Asn195Ile. In obese non-diabetic subjects, the two promoter polymorphisms were associated with higher fasting glucose concentrations (p=0.006 andp=0.0004, for −765 4G/5G and −844 A>G, respectively) and insulin (p=0.05 and p=0.008, for −765 4G/5G and −844 A>G, respectively). Moreover, the −844 A>G SNP was associated with lower triglyceride (p=0.002) and higher HDL cholesterol concentrations (p=0.02) in lean subjects. In addition, the two promoter and Ala15Thr polymorphisms showed a trend towards association with CHD in diabetic subjects (-765 4G/5G: 0.56/0.51, p=0.05; −844A>G: 0.63/0.57, p=0.02; Ala15Thr: 0.91/0.88, p=0.04). The SNPs Ala15Thr, located in the PAI-1 signal peptide, and rare the Asn195Ile, located in a β-sheet structure, could influence conformation of these two structures. Conclusions/interpretation. Our results support the hypothesis that PAI-1 polymorphisms probably interact with known environmental risk factors (chronic hyperglycaemia, obesity, etc.) to induce a more severe insulin-resistant metabolic profile in overweight subjects, and to further increase risk for CHD in diabetic subjects. [Diabetologia (2003[Diabetologia ( ) 46:1284[Diabetologia ( -1290 Keywords PAI-1, obesity, metabolic syndrome, CHD, fasting glucose, insulin, triglycerides, HDL, Type 2 diabetes mellitus.

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“…The two known promoter polymorphisms showed similar frequencies as previously reported in other Caucasian populations [24,26].…”

Section: Resultssupporting

confidence: 85%

Section: Resultssupporting

confidence: 75%

“…All the polymorphisms were in Hardy-Weinberg equilibrium (Table 1), except the −844 A>G variant which differed significantly (χ 2 =5.49, p=0.02), as was previously described [26].…”

Section: Resultssupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

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PAI-1 polymorphisms modulate phenotypes associated with the metabolic syndrome in obese and diabetic Caucasian population

et al. 2003

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“…About second polymorphism −844 G/A, we don't found relationship between this polymorphism and PAI-1 level, this results is in agreement with the literature [11] [12] [27].…”

Section: Resultssupporting

confidence: 91%

Genetic and Metabolic Determinants of Plasminogen Activator Inhibitor 1 (PAI-1) in Tunisian Type 2 Diabetes Patients

Moustapha¹,

Chadhli-Chaieb²,

Mahjoub³

et al. 2017

OJEMD

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Background: PAI-1 (plasminogen activator inhibitor-1) is a powerful regulator of fibrinolysis and plasma level is high in type 2 diabetes and cardio-vascular disease, which is determined by genetic polymorphisms in PAI-1 gene and environmental factors. The aim of the study was to examine the determinants of plasma PAI-1 Ag level among type 2 diabetes patients. Methods: 491 Tunisian type 2 diabetes patients had clinical evaluation (weight, high, BMI, Waist Circumference), laboratory investigations including FBG Hb1Ac, cholesterol, triglyceride; HDL-cholesterol was done; plasma PAI-1 antigen level was done with ELISA; −675 4G/5G and −844 G/A polymorphisms of PAI-1 gene was done by PCR-ASA and PCR-RFLP respectively. Results: The mean age for our patients was 58.3 ± 10.5 years; sex-ratio = 0.92; mean PAI-1 level was 34.6 ± 21.3 ng/ml. We didn't find correlation between PAI-1 level and BMI, but we have found significant correlation between PAI-1 and waist circumference (p = 0.032), most enhanced in men (P = 0.002), T2D patients who have FBG > 11 mmol/l had PAI-1 Ag level higher than those who have FBG < 11 mmol/l (P = 0.034), but no difference found between T2D with high Hb1Ac > 8% and those with Hb1Ac < 8%, significant correlation was seen between PAI-1 level and LDL-cholesterol (P = 0.05), high correlation between PAI-1 Ag level and −675 4G/5G polymorphism genotype was seen, 4G/4G carriers had the highest PAI-1 level, 4G/5G had intermediary level and 5G/5G had the lowest level (P < 0.001). No correlation was seen between PAI-1 Ag level and −844G/A polymorphism genotypes. Using multiple variable linear regression analysis, the independent factor associated with plasma PAI-1 level was −675 4G/5G polymorphism (regression coefficient β = 4.6, P

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The plasminogen activator inhibitor 1 4G/5G polymorphism is not associated with longevity: a study in octogenarians

et al. 2001

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Accumulating evidence suggests that plasma levels of the plasminogen activator inhibitor 1 (PAI-1) may modulate the risk of coronary artery disease. The regulation of PAI-1 levels underlies not only environmental but also genetic influences. The 4G/5G polymorphism of the PAI-1 gene has recently gained additional relevance as a possible cardiovascular risk factor, as the 4G allele may be associated with enhanced expression of the PAI-1 gene. This retrospective cohort study examined the effect of the PAI-1 4G/5G genotype on longevity among 205 subjects aged 80 years and older. Such studies in larger cohorts have recently become available along with new methods for the rapid and easy determination of gene polymorphisms. We utilized a light-cycler assisted method which is a fast and flexible method of analyzing the PAI-1 4G/5G polymorphism on the gene level. In these 205 persons the 4G/5G allele was found in 96 persons (47%), the 4G/4G variant in 62 (30%), and the 5G/5G allele in 47 (23%). These data are similar to the allele distribution described in other large cohorts not restricted to old age. Thus the results of this study are not suggestive of an important contribution of the PAI-1 genotype on total mortality.

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A Novel G/a and the 4g/5g Polymorphism Within the Promoter of the Plasminogen Activator Inhibitor-1 Gene in Patients With Deep Vein Thrombosis

Cited by 88 publications

References 21 publications

PAI-1 polymorphisms modulate phenotypes associated with the metabolic syndrome in obese and diabetic Caucasian population

PAI-1 polymorphisms modulate phenotypes associated with the metabolic syndrome in obese and diabetic Caucasian population

Genetic and Metabolic Determinants of Plasminogen Activator Inhibitor 1 (PAI-1) in Tunisian Type 2 Diabetes Patients

The plasminogen activator inhibitor 1 4G/5G polymorphism is not associated with longevity: a study in octogenarians

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