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PubMed | Research Unit UR 12ES09 Dyslipidemia and Atherogenesis, University of Sfax and University of Monastir
Type: | Journal: Lipids in health and disease | Year: 2016

Angiopoietin-like protein 4 (ANGPTL4) is a metabolic factor that increases plasma triglyceride levels by inhibiting lipoprotein lipase (LPL). The objective of this study was to investigate the association of ANGPTL4 variants (E40K and T266M) with triglyceride levels and with cardiovascular risk factors, such as metabolic syndrome (MetS) and obesity in type 2 diabetic Tunisian population.We investigated the effect of the tagging single nucleotide polymorphisms (SNPs) rs1044250 (T266M) and rs116843064 (E40K) with triglyceride (TG) levels and CAD risk factors in a cohort of 220 patients undergoing coronary angiography for the evaluation of stable CAD, all of whom had (type 2 diabetes) T2D and were at least overweight. Multivariate logistic regressions were performed on association studies.TT genotype of rs1044250 (T266M variant) showed a protective effect on CVD risk in CAD group patients (OR 1.92, 95% CI 0.601.42, p =0.05) compared with control Group patients (OR 1.17, 95% CI 0.70-1.66, p = 0.72). Likewise, GA genotype of rs116843064 (E40K variant): (OR 0.74, 95% CI 0.54-1.65, p =0.01) for the CAD group compared with control Group patients (OR 1.12, 95% CI 0.68-1.74, p = 0.074).ANGPTL4 variants are associated with, not only lower fasting triglyceride levels, but also a decreased cardiovascular risk in T2D Tunisian patients. So, T266M and E40K polymorphism predicts cardiovascular disease risk in Type 2 diabetic Tunisian population.


Chehaibi K.,Research Unit UR 12ES09 Dyslipidemia and Atherogenesis | Nouira S.,CHU Fattouma Bourguiba | Mahdouani K.,Ibn Eljazzar Hospital | Hamdi S.,Fattouma Bourguiba Hospital | And 2 more authors.
Journal of Molecular Neuroscience | Year: 2014

Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor involved in the regulation of lipid metabolism, diabetes, obesity, atherogenesis and inflammation. PPARγ genetic variation has been associated with metabolic and cardiovascular diseases. The aim of this study was to explore, for the first time, the relationship between PPARγ C161T polymorphism and the risk of ischemic stroke (IS) among patients with type 2 diabetes mellitus (T2DM). A total of 196 patients with IS (117 diabetics and 79 nondiabetics) and 192 controls were recruited to enroll in this study. PPARγ C161T genotyping was performed by PCR-RFLP technique. The 161T allele as compared with C allele was found to be higher in controls than in IS patients (with or without T2DM). After adjusting for multiple risk factors, the T allele carriers had significantly reduced IS risk (OR = 0.575, 95 % CI 0.348–0.951, p = 0.030) compared to the CC homozygotes which increased significantly the risk in IS patients with T2DM (OR = 1.85, 95 % CI 1.23–2.62). Moreover, the triglycerides (TG) and ApoB levels in CC homozygote carriers were significantly higher than those in T allele carriers. These results indicate that the C161T of PPARγ may reduce the risk of IS by modulation of adipose metabolism especially TG and ApoB in IS patients with T2DM. © 2014, Springer Science+Business Media New York.


Chehaibi K.,Research Unit UR 12ES09 Dyslipidemia and Atherogenesis | Hrira M.Y.,Research Unit UR 07 06 | Nouira S.,CHU Fattouma Bourguiba | Maatouk F.,Fattouma Bourguiba Hospital | And 2 more authors.
Journal of the Neurological Sciences | Year: 2014

Matrix metalloproteinases (MMPs) play an important role in early atherosclerosis, extracellular matrix remodeling, plaque rupture and myocardial infarction. MMP gene polymorphisms contribute to the risk of developing cardiovascular diseases. In this study, we investigated, for the first time, the association between MMP-1-16071G/2G, MMP-12 -82A/G and MMP-12 1082A/G genotypes and haplotypes and the risk of ischemic stroke (IS) among patients with type 2 diabetes mellitus (T2DM). To examine whether these genetic polymorphisms are associated with susceptibility to IS, 196 patients with IS and 192 controls were examined by PCR-based RFLP. When the analyses were adjusted for multiple risk factors, no interaction between T2DM and MMP-1-1607 1G/2G polymorphism on the risk of ischemic stroke was found (p = 0.074). However, MMP-12 polymorphisms genotypes were associated with the higher risk of IS in diabetic patients compared with total patients. The -82G-1082G haplotype of MMP-12 polymorphisms was associated with higher risk of ischemic stroke in diabetic patients [AOR = 2.33; 95% CI (1.25-3.62), P = 0.032]. These findings showed that there was an important joint effect of the MMP-12 polymorphisms and T2DM on the risk of IS and therefore it can be considered as a potential marker of cerebrovascular disorders in diabetic patients. © 2014 Elsevier B.V. All rights reserved.


Slimani A.,Research Unit UR 12ES09 Dyslipidemia and Atherogenesis | Harira Y.,University of Monastir | Trabelsi I.,Research Unit UR 12ES09 Dyslipidemia and Atherogenesis | Jomaa W.,Fattouma Bourguiba Hospital | And 3 more authors.
Journal of Molecular Neuroscience | Year: 2014

The association of E670G (rs505151) polymorphism in PCSK9 gene with an increased risk of coronary artery disease (CAD) and ischemic stroke (IS) was reported in previous studies. We investigated the effect of the E670G (rs505151) on the risk of CAD and IS in a Tunisian cohort. Genotyping of the PCSK9 E670G was performed using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) and then confirmed by direct sequencing. The frequency of the 670G allele was significantly higher in the CAD than in the no-CAD subgroup (0.132 vs. 0.068, p=0.030). As expected, the incidence of E670G was significantly important in IS subgroup than control group (0.122 vs. 0.073, p=0.032). Furthermore in CAD patients, the 670G carriers showed significantly increased plasma total cholesterol and LDL-cholesterol levels compared to E670 carriers (6.78 [6.47-7.00] vs. 4.92 [4.02-5.46] mmol/l, p<0.0001 and 4.60 [4.00-5.04] vs. 3.00 [2.22-3.70] mmol/l p=0.001, respectively). The risk and severity of CAD were significantly increased in 670G carriers between no-CAD subgroup and CAD patients presenting a stenosis ≥50 % in two or three major coronary arteries (0.068 vs. 0.198, p=0.001, OR=3.39 [1.55-7.37]). The E670G polymorphism of the PCSK9 gene is mainly associated with a increased risk and severity of CAD and IS in Tunisian cohort. © 2014 Springer Science+Business Media.


PubMed | Fattouma Bourguiba Hospital, University of Versailles, French Institute of Health and Medical Research, University Pierre and Marie Curie and 2 more.
Type: Journal Article | Journal: Molecular and cellular probes | Year: 2015

The c.61_63dupCTG (L10) allele of rs72555377 polymorphism in PCSK9 has been reported to be associated with low-density lipoprotein-cholesterol (LDL-C) levels and with a decreased risk of coronary artery disease (CAD). We investigated the effect of two known alleles for rs72555377, L10 and L11, on the risk of CAD in a Tunisian cohort (218 patients diagnosed by angiography and 125 control subjects). Two subgroups of patients were defined by their level of stenosis: 50% for CAD and <50% for no-CAD. The genotypes were obtained by the size measurement of fluorescent-labeled PCR products. We identified a novel allele for the rs72555377 polymorphism: an in-frame deletion, c.61_63delCTG (L8). The frequency of the L10 allele was significantly higher in the no-CAD subgroup than in the CAD subgroup (0.210 vs 0.114, p=0.045), and than in the subgroup of CAD patients presenting a stenosis 50% in two or three major coronary arteries (0.210 vs 0.125, p=0.028). Multiple regression analysis showed that the L10 allele was significantly associated with a reduced risk of CAD (p=0.049, OR=0.51[0.26-1.00]), and with its reduced severity (p=0.045, OR=0.44[0.20-0.98]). The L10 allele is associated with a reduced risk and severity of CAD, seemingly independently of its LDL-lowering effect, suggesting a direct effect of PCSK9 on atherogenesis.


Najah M.,Research Unit UR 12ES09 Dyslipidemia and Atherogenesis | Youssef S.M.,Research Unit UR 12ES09 Dyslipidemia and Atherogenesis | Yahia H.M.,Research Unit 07 UR 06 | Afef S.,Research Unit UR 12ES09 Dyslipidemia and Atherogenesis | And 5 more authors.
Diagnostic Pathology | Year: 2013

Background: Abetalipoproteinemia (ABL; OMIM 200100) is a rare monogenic disorder of lipid metabolism characterized by reduced plasma levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and almost complete absence of apolipoprotein B (apoB). ABL results from genetic deficiency in microsomal triglyceride transfer protein (MTP; OMIM 157147). In the present study we investigated two unrelated Tunisian patients, born from consanguineous marriages, with severe deficiency of plasma low-density lipoprotein (LDL) and apo B. Methods: Intestinal biopsies were performed and The MTTP gene was amplified by Polymerase chain reaction then directly sequenced in patients presenting chronic diarrhea and retarded growth. Results: First proband was homozygous for a novel nucleotide deletion (c. 2611delC) involving the exon 18 of MTTP gene predicted to cause a non functional protein of 898 amino acids (p.H871I fsX29). Second proband was homozygous for a nonsense mutation in exon 8 (c.923 G > A) predicted to cause a truncated protein of 307 amino acids (p.W308X), previously reported in ABL patients. Conclusions: We discovered a novel mutation in MTTP gene and we confirmed the diagnosis of abetalipoproteinemia in new Tunisian families. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8134027928652779. © 2013 Najah et al.; licensee BioMed Central Ltd.


PubMed | Research Unit UR 12ES09 Dyslipidemia and Atherogenesis and University of Monastir
Type: Journal Article | Journal: International journal of clinical and experimental medicine | Year: 2015

Activity of the renin-angiotensin Aldosterone system is increased in patients with heart failure (HF). The Angiotensinogen gene and specifically M235T polymorphism has been linked to susceptibility to hypertension, coronary heart disease and atrial fibrillation. Its role in heart failure is not yet sufficiently demonstrated. The aim of the present study was to assess the association between rs699 (M235T) polymorphism and heart failure in terms of diagnosis and prognosis. We included all patients over 20 years old consulting in the Emergency Department for acute dyspnea. According to the results of the B-type natriuretic peptide (BNP level), patients were divided into two groups: HF and non-HF group. DNA study was performed for all subjects and their genotypes were identified as TT, CT or CC. Mortality was followed for one year. We included 234 patients. We found the diagnosis of HF in 73 patients out of 160 (45%). Our results showed that the frequency of the T allele was higher in HF group patients than in non-HF group (69% vs. 33%, P<0.01). Patients carrying the TT and CT genotypes had a higher proportion of HF than those carrying the CC genotype (respectively 53% and 31% vs. 15%, P<0.01). According to multivariate analysis, TT genotype presented the highest risk of HF (OR=4.9 95% CI: 2.12-9.1) and the highest risk of death (OR=6.45 95% CI: 3.6-16.4) compared to the other two genotypes. The current study suggests that M235T polymorphism might be associated with increased risk of both HF and death.


PubMed | University of Nice Sophia Antipolis, Research Unit UR 12ES09 Dyslipidemia and Atherogenesis and Autonomous University of Barcelona
Type: | Journal: Translational research : the journal of laboratory and clinical medicine | Year: 2016

The systemic response to ischemic stroke is associated with the hepatic acute phase response (APR) that modulates leukocytes recruitment to the injured brain. The inappropriate recruitment of leukocytes to the brain parenchyma can result in blood-brain barrier (BBB) breakdown. Emerging data suggest that peroxisome proliferator-activated receptor beta/delta (PPAR-/) activation has a potential neuroprotective role in ischemic stroke. However, mechanisms of PPAR-/ mediated protection in ischemic insults remain unclear. In the present study, we determined for the first time, the effects of GW0742, a PPAR-/ agonist on the APR following brain injury and assessed the effects on BBB permeability and tight junction integrity via claudin-5, occludin, and zona occludens-1 expression. C57/BL6 mice were exposed to 1hour of ischemia and received 10 minutes before reperfusion either a vehicle solution or GW0742. Hepatic expression of chemokines (C-X-C motif ligand: CXCL1, CXCL2, and CXCL10), serum amyloid A-1, tumor necrosis factor alpha, interleukin-1, and interleukin-6 was measured, and the extent of brain and hepatic neutrophil infiltration was determined. The results showed that GW0742 treatment decreased infarct volume and edema, reactant production and neutrophil recruitment to the brain and liver, which is a hallmark of the APR. GW0742 significantly reduced BBB leakage and metalloproteinase 9 expression and upregulated the expression of tight junction proteins. These findings may help to guide the experimental and clinical therapeutic use of PPAR-/ agonists against brain injury.


PubMed | Research Unit UR 12ES09 Dyslipidemia and Atherogenesis and Ibn Eljazzar Hospital
Type: Journal Article | Journal: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association | Year: 2016

Ischemic stroke (IS) usually initiates inflammation and oxidative stress leading to neuronal death. Diabetes and impaired fasting glucose are associated with incidence of cerebrovascular and cardiovascular diseases.In the present study, we assessed the relationship of fasting glucose with antioxidative parameters (erythrocyte glutathione peroxidase [GPx] and superoxide dismutase [SOD] activities) and inflammatory markers (high-sensitivity C-reactive protein [hs-CRP] and fibrinogen) in IS patients with and without type 2 diabetes mellitus (T2DM). In addition, we determined factors associated with the risk of IS among these patients. Antioxidative, inflammatory, and lipid parameters were measured in 196 patients with IS (117diabetics and 79 nondiabetics).After adjustment of covariates, multiple logistic regression analysis showed that SOD and GPx significantly decreased the risk of IS among patients with and without T2DM. However, hs-CRP increased the risk of IS. For the diabetic patients, fasting glucose was positively correlated with hs-CRP and fibrinogen and was negatively correlated with GPx and SOD levels. In addition, fasting glucose and hemoglobin A1c or glycosylated hemoglobin (HbA1c) have been shown to increase the risk of IS in diabetic patients.These data suggest that the antioxidant activity of plasma may be an important factor that provides protection from IS. hs-CRP concentrations can be used as a clinical screening tool to identify individuals with higher risk of IS. Finally, fasting glucose and HbA1c may also be useful indicators for cerebrovascular risk in diabetic patients that may be mediated by low levels of antioxidative defense markers and high inflammation status.


PubMed | Research Unit UR 12ES09 Dyslipidemia and Atherogenesis
Type: Journal Article | Journal: Journal of molecular neuroscience : MN | Year: 2013

PPAR +294T/C polymorphism was investigated in diabetics, in normolipidemic healthy controls, in dyslipidemic and nondyslipidemic coronary artery disease patients but never in ischemic stroke patients. The aim of this study was to explore, for the first time, the relationship between the genetic polymorphism of PPAR and the risk of ischemic stroke among patients with diabetes. The study group consisted of 196 patients with ischemic stroke and 192 controls. Plasma concentrations of total cholesterol, triglycerides, low-, and high-density lipoprotein did not differ significantly between subjects carrying the TT genotype and those carrying the CC/TC genotype in both ischemic stroke patients (with or without diabetes) and control groups. The +294C allele (CC + CT genotypes) as compared with TT genotypes was found to be higher in total ischemic stroke patients than in controls. On the other hand, no interaction between diabetes and PPAR +294T/C polymorphism on the risk of ischemic stroke was found (p=0.089). The PPAR +294T/C polymorphism was associated with the risk of ischemic stroke in Tunisian subjects. This polymorphism has no influence on plasma lipoprotein concentrations and body mass index either in healthy subjects or in ischemic stroke patients with or without diabetes both in males and females.

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