Contribution of Genetic and Metabolic Syndrome to Omental Adipose Tissue PAI-1 Gene mRNA and Plasma Levels in Obesity

Bouchard, Luigi; Vohl, Marie‐Claude; Lebel, Stéfane; Hould, Frédéric‐Simon; Marceau, Picard; Bergeron, Jean; Pérusse, Louis; Mauriège, Pascale

doi:10.1007/s11695-010-0079-1

Cited by 19 publications

(8 citation statements)

References 34 publications

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“…These results obtained in our study are similar to those reported in a previous study done in Caucasian population in which A/A genotype was associated with the susceptibility of developing MetS (OR, 4.87; p < 0.001) [12]. These consistent results reported in different populations may be due to the effect of the polymorphism on the levels of the protein, since it has been reported that the base change of G to A at position -844 of the promoter PAI-1 gene generates a binding site consensus sequence for Ets nuclear protein, which could be involved in regulating gene expression and influencing the increase in PAI-1 plasma protein levels [32,33].…”

Section: Discussionsupporting

confidence: 92%

“…On the other hand, the -844 G/A polymorphism we observed that is distributed inversely to those reported in Caucasian populations, in which the A allele is more frequent than the G allele [12,18,19]. In our study this polymorphism had a high frequency of G allele and a lower frequency of A allele, consistent with already reported frequencies in previous studies in Mexican mestizo population [20,30], suggesting that in the Mexican population there is a high frequency of allele G.…”

Section: Discussionmentioning

confidence: 56%

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Relationship of metabolic syndrome and its components with -844 G/A and HindIII C/G PAI-1 gene polymorphisms in Mexican children

et al. 2012

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BackgroundSeveral association studies have shown that -844 G/A and HindIII C/G PAI-1 polymorphisms are related with increase of PAI-1 levels, obesity, insulin resistance, glucose intolerance, hypertension and dyslipidemia, which are components of metabolic syndrome. The aim of this study was to analyze the allele and genotype frequencies of these polymorphisms in PAI-1 gene and its association with metabolic syndrome and its components in a sample of Mexican mestizo children.MethodsThis study included 100 children with an age range between 6-11 years divided in two groups: a) 48 children diagnosed with metabolic syndrome and b) 52 children metabolically healthy without any clinical and biochemical alteration. Metabolic syndrome was defined as the presence of three or more of the following criteria: fasting glucose levels ≥ 100 mg/dL, triglycerides ≥ 150 mg/dL, HDL-cholesterol < 40 mg/dL, obesity BMI ≥ 95th percentile, systolic blood pressure (SBP) and diastolic blood pressure (DBP) ≥ 95th percentile and insulin resistance HOMA-IR ≥ 2.4. The -844 G/A and HindIII C/G PAI-1 polymorphisms were analyzed by PCR-RFLP.ResultsFor the -844 G/A polymorphism, the G/A genotype (OR = 2.79; 95% CI, 1.11-7.08; p = 0.015) and the A allele (OR = 2.2; 95% CI, 1.10-4.43; p = 0.015) were associated with metabolic syndrome. The -844 G/A and A/A genotypes were associated with increase in plasma triglycerides levels (OR = 2.6; 95% CI, 1.16 to 6.04; p = 0.02), decrease in plasma HDL-cholesterol levels (OR = 2.4; 95% CI, 1.06 to 5.42; p = 0.03) and obesity (OR = 2.6; 95% CI, 1.17-5.92; p = 0.01). The C/G and G/G genotypes of the HindIII C/G polymorphism contributed to a significant increase in plasma total cholesterol levels (179 vs. 165 mg/dL; p = 0.02) in comparison with C/C genotype.ConclusionsThe -844 G/A PAI-1 polymorphism is related with the risk of developing metabolic syndrome, obesity and atherogenic dyslipidemia, and the HindIII C/G PAI-1 polymorphism was associated with the increase of total cholesterol levels in Mexican children.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 56%

Relationship of metabolic syndrome and its components with -844 G/A and HindIII C/G PAI-1 gene polymorphisms in Mexican children

et al. 2012

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“…We also did not find a relationship between the expression of fibrinolytic regulators in adipose tissue and BMI. This finding is in agreement with the study by Bouchard [18], but not with the findings of Alessi [8]. The differences between patients with and without DM could not be confirmed in our study due the small sample size, although it has been reported that hyperglycemia can lead to the increased expression of PAI-1 in adipose tissue [19].…”

Section: Fibrinolytic System Components In Peritoneal Membrane and Thsupporting

confidence: 80%

“…Profibrotic factor TGF-β is also produced by mesothelial cells influenced by peritoneal dialysis fluids [18]. TGF-α, IL-6 and TGF-β are known as modulators of PAI-1 expression.…”

Section: Inflammatory Products Of Adipocytesmentioning

confidence: 99%

Adipocytes derived fibrinolytic components in peritoneum — a pilot study

Opatrná

Korabečná²,

Křížková

et al. 2012

Open Medicine

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AbstractThe proteins of the fibrinolytic system — urokinase plasminogen activator(uPA), tissue plasminogen activator (tPA)and plasminogen activator inhibitor type IPAI-I) — play important roles in fibrotization in various organs and including peritoneum. To study the cellular localization of PAI-1, tPA and uPA within the adipose tissue of the peritoneal membrane in patients at the onset of peritoneal dialysis(PD) we determined the initial expression of these proteins in relationship to multiple clinical variables. Methods: routinely performed parietal peritoneal biopsies in 12 patients undergoing peritoneal catheter implantation were examined. We used formalinfixed, paraffin-embedded specimens for immunohistochemical localization of these proteins along with the stereological pointcounting method for quantification of their expression within the peritoneal adipose tissue. Results: strong positive mutual correlation between the expression of PAI-1 and both uPA (SpearmanR=0.66) and tPA (R=0.59) as well as between the expression of uPA and tPA (R=0.77) was found without any relatioship to BMI, age, peritoneal transport characteristic or diabetes status. Conclusion: Adipose tissue within the peritoneum is capable of producing fibrinolysis regulators (independently on clinical parameters) thus possibly affecting the fibrotization and function of peritoneum as dialysis membrane. The effect of dialysis solution dosing, composition and other dialysis related factors should be clarified in future studies.

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“…There are different PAI-1 polymorphisms of clinical importance described previously by various researchers. The most commonly described ones are the following: PAI-1 (rs1799889) -675 4G/5G insertion/deletion polymorphism at -675 in the promoter region [ 10 ], G-A substitution at position -844 (rs2227631) [ 11 , 12 ], c.43G<A (p.A15T, rs6092), and (p.I17V, rs 6090) [ 13 ]. It has been stated that different polymorphisms result in different levels of PAI-1 concentrations.…”

Section: Introductionmentioning

confidence: 99%

The Effect of PAI-1 4G/5G Polymorphism and Clinical Factors on Coronary Artery Occlusion in Myocardial Infarction

et al. 2015

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Objective. Data on the impact of PAI-1-675 4G/5G genotype for fibrinolysis during myocardial infarction are inconsistent. The aim of our study was to evaluate the association of clinical and genetic (PAI-1-675 4G/5G polymorphism) factors with coronary artery occlusion in patients with myocardial infarction. Materials and Methods. PAI-1-675 4G/5G detection was achieved by using Sanger sequencing in a sample of patients hospitalized for stent implantation due to myocardial infarction. We categorized the patients into two groups: patients with coronary artery occlusion and patients without coronary artery occlusion according to angiographic evaluation. Results. We identified n = 122 (32.4%) 4G/4G, n = 186 (49.5%) 4G/5G, and n = 68 (18.1%) 5G/5G PAI-1 genotype carriers. Univariate and multivariate analysis showed that only the 4G/5G genotype was associated with coronary artery occlusion (OR: 1.656 and 95% CI: 1.009–2.718, p = 0.046). Conclusions. Our results showed that carriers of PAI-1 4G/5G genotype with myocardial infarction have increased odds of coronary artery occlusion more than 1.6 times in comparison to the carriers of homozygous genotypes.

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Contribution of Genetic and Metabolic Syndrome to Omental Adipose Tissue PAI-1 Gene mRNA and Plasma Levels in Obesity

Abstract: These results suggest that PAI-1 polymorphisms contribute significantly to PAI-1 plasma levels but do not support the notion that omental AT is one of its major source.

Cited by 19 publications

References 34 publications

Relationship of metabolic syndrome and its components with -844 G/A and HindIII C/G PAI-1 gene polymorphisms in Mexican children

Relationship of metabolic syndrome and its components with -844 G/A and HindIII C/G PAI-1 gene polymorphisms in Mexican children

Adipocytes derived fibrinolytic components in peritoneum — a pilot study

The Effect of PAI-1 4G/5G Polymorphism and Clinical Factors on Coronary Artery Occlusion in Myocardial Infarction

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