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

Lopes, Ceci Mendes Carvalho; Dina, Christian; Durand, Emmanuelle; Froguel, Philippe

doi:10.1007/s00125-003-1170-0

Cited by 60 publications

(46 citation statements)

References 46 publications

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“…Lopes et al (84) analyzed genetic contributions of PAI-1 mutations to the diabetes and to its complications for over 1,000 unrelated individuals of a French Caucasian cohort, selected for diabetes and obesity. They were looking for an association between PAI-1 polymorphisms and phenotypes related to diabetes.…”

Section: Diabetic Vascular Disease and Pai-1mentioning

confidence: 99%

“…The authors found five SNP variants of which two promoter polymorphisms were associated with higher fasting glucose concentrations (P=0.006 and P=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) (84). They suggest that PAI-1 polymorphisms probably induce a more severe insulin-resistant metabolic profile in diabetes, and further increase the risk for coronary heart disease in diabetic patients (84).…”

Section: Diabetic Vascular Disease and Pai-1mentioning

confidence: 99%

See 1 more Smart Citation

Can inactivators of plasminogen activator inhibitor alleviate the burden of obesity and diabetes? (Review)

Jankun

Al-Senaidy²,

Skrzypczak‐Jankun³

2011

Int J Mol Med

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Section: Diabetic Vascular Disease and Pai-1mentioning

confidence: 99%

Section: Diabetic Vascular Disease and Pai-1mentioning

confidence: 99%

Can inactivators of plasminogen activator inhibitor alleviate the burden of obesity and diabetes? (Review)

Jankun

Al-Senaidy²,

Skrzypczak‐Jankun³

2011

Int J Mol Med

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“…One way to verify this hypothesis is to look for a relation between single nucleotide polymorphisms (SNPs) influencing PAI-1 expression or activity, MI, and parameters belonging to the MetS. Several SERPINE1 (formerly PAI-1) gene SNPs have been identified, [21][22][23] among which the polymorphism 4G/5G (rs1799889) located in position Ϫ675 of the promoter region has been quite extensively studied. The 4G allele has been shown to be associated with increased SERPINE1 transcription compared with the 5G allele in in vitro studies 21,24 and with increased plasma PAI-1 levels in vivo.…”

mentioning

confidence: 99%

Association of Plasminogen Activator Inhibitor (PAI)-1 (SERPINE1) SNPs With Myocardial Infarction, Plasma PAI-1, and Metabolic Parameters

Morange

Saut

Alessi

et al. 2007

ATVB

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Objective-The purpose of this study was to investigate the effects of plasminogen activator inhibitor-1 (PAI-1) gene (SERPINE1) single nucleotide polymorphisms (SNPs) on the risk of myocardial infarction (MI), on PAI-1 levels, and factors related to the metabolic syndrome. Methods and Results-Eleven SNPs capturing the common genetic variation of the SERPINE1 gene were genotyped in the HIFMECH study. In the 510 male cases and their 543 age-matched controls, a significant gene-smoking interaction was observed. In nonsmokers, the rs7242-G allele was more frequent in cases than in controls (0.486 versus 0.382, Pϭ0.013) whereas the haplotype derived from the rs2227631 (Ϫ844AϾG)-G and rs2227683-A alleles was Ϸ3-fold lower in cases than in controls (0.042 versus 0.115, Pϭ0.006). SERPINE1 haplotypes explained 3.5% (Pϭ0.007) of the variability of PAI-1 levels, which was attributable to the combined effects of 3 SNPs, Ϫ844AϾG, rs2227666, and rs2227694. The rs6092 (Ala15Thr) and rs7242 SNPs acted additively to explain 4.4% of the variability of plasma insulin levels and 1.6% of the variability of BMI (PϽ10 Ϫ3 and Pϭ0.023, respectively). Conclusions-SERPINE1 haplotypes are mildly associated with plasma levels of PAI-1 and with the risk of MI in nonsmokers. They are also associated with insulin levels and BMI. (Arterioscler Thromb Vasc Biol.

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“…The promoter's two polymorphisms and the polymorphism Ala15Thr also showed association with CVD in diabetic persons (-765 4G/5G: 0.56/0.51, p=0.05; -844 A>G: 0.63/0.57, p=0.02; Ala15Thr: 0.91/0.88, p=0.04). In summary, these polymorphisms increase the risk of CVD in diabetic individuals (102).…”

Section: Decrease Of Fibrinolysismentioning

confidence: 97%

Hemostasis alterations in metabolic syndrome (Review)

Palomo¹,

Alarcón²,

Moore‐Carrasco³

et al. 2006

Int J Mol Med

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Abstract. Metabolic syndrome (MS) is characterized by the presence of at least three of the following alterations: enlargement of the waist diameter, higher levels of arterial pressure, low density lipoprotein cholesterol and glycemia, and reduction of high density lipoprotein cholesterol. The prevalence of MS reaches 23% in young adults, a percentage that increases with age. People with MS have a greater risk of suffering from cardiovascular disease (CVD). The physiopathologic alterations now found to exist in MS are diverse; among them is endothelial dysfunction, which triggers atherogenic lesions and hypercoagulability characterized by alterations of the coagulation factors and the regulatory proteins of fibrinolysis such as the plasminogen activator inhibitor (PAI-1). The increase in oxidative stress and/or the reactive oxygen species in patients with MS is partially related to the oxidation state of the lipoproteins, especially of the low density lipoproteins. This fact favors atherogenesis. Moreover, the oxidative stress produces alterations in the production of adipokines, cytokines secreted by the adipose tissues. The abnormality in the transport of lipoprotein diminishes the catabolism of the very low density lipoprotein (VLDL) and increases the catabolism of the high density lipoprotein (HDL), which creates insulin resistance. This process is associated with a lower concentration of adiponectin that in turn regulates the catabolism of VLDL and HDL; consequently increasing the flow of fatty acids from the adipose tissue to the liver and muscles. The proinflammatory cytokines, among them tumor necrosis factor · (TNF-·), are of great importance in MS regulating different processes and molecules such as PAI-1. PAI-1 is controlled by the group of transcription factors peroxisome proliferator-activated receptor (PPAR), especially by PPAR Á and · ligands. In summary, MS includes multiple alterations related to insulin resistance at several levels: hepatic, muscular, adipose and vascular tissue (endothelium). The exact mechanism that underlies the relationship between MS and CVD are not sufficiently known yet; pathogenic explanations are lacking for the mechanisms relating metabolic factors to insulin resistance and the association with the development of atherosclerosis and thrombosis. MS alterations and the main aspects related to homeostasis alterations are examined in this report.

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

Cited by 60 publications

References 46 publications

Can inactivators of plasminogen activator inhibitor alleviate the burden of obesity and diabetes? (Review)

Can inactivators of plasminogen activator inhibitor alleviate the burden of obesity and diabetes? (Review)

Association of Plasminogen Activator Inhibitor (PAI)-1 (SERPINE1) SNPs With Myocardial Infarction, Plasma PAI-1, and Metabolic Parameters

Hemostasis alterations in metabolic syndrome (Review)

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