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Menzel Bourguiba, Tunisia

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. Source

Chehaibi K.,Research Unit UR 12ES09 Dyslipidemia and Atherogenesis | Nouira S.,CHU Fattouma Bourguiba | Mahdouani K.,Molecular Biology Laboratory | 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. Source

Turki A.,University of Monastir | Al-Zaben G.S.,Arabian Gulf University | Mtiraoui N.,University of Monastir | Marmmuoch H.,CHU Fattouma Bourguiba | And 2 more authors.
Gene | Year: 2013

Genome-wide association studies validated transcription factor 7-like 2 (TCF7L2) gene as confirmed type 2 diabetes (T2DM) susceptibility locus, and an ethnic contribution of TCF7L2 variants to T2DM risk was indicated. The aim of this study was to replicate in a Tunisian Arab population identified associations of common TCF7L2 variants with T2DM. We tested the association of TCF7L2 variants: rs4506565, rs7903146, rs12243326, and rs12255372, with T2DM in 900 Tunisian patients and 875 control subjects. TCF7L2 genotyping was done by allelic discrimination/real-time PCR method. Minor allele frequencies of rs4506565 (P=2.4×10-8), rs7903146 (P=1.2×10-6), rs12243326 (P=8.4×10-8) and rs12255372 (P=1.1×10-5) were significantly higher in cases. The four tested TCF7L2 variants were in linkage disequilibrium, and 4-locus (rs4506565, rs7903146, rs12243326, rs12255372) haplotype analysis demonstrated that haplotype 1111 was negatively associated (Pc<0.001), while haplotypes 2222 (Pc=0.008) and 2211 (Pc=0.020) were positively associated with T2DM risk, after controlling for a number of covariates. The strong contribution of TCF7L2 gene variants to T2DM among Tunisians is in line with similar findings in other ethnic groups, confirming TCF7L2 as a common T2DM candidate gene. © 2012 Elsevier B.V. Source

Turki A.,Research Unit of Biology and Genetics of Cancer and Haematological and Autoimmune Diseases | Mahjoub T.,Research Unit of Biology and Genetics of Cancer and Haematological and Autoimmune Diseases | Mtiraoui N.,Research Unit of Biology and Genetics of Cancer and Haematological and Autoimmune Diseases | Mtiraoui N.,University of Monastir | And 3 more authors.
Gene | Year: 2013

Previous studies and replication analyses have linked chromosome 18q21.1-23 with type 2 diabetes (T2DM) and its complications, including diabetic nephropathy (DN). Here we investigated the association of POL1-nearby variant rs488846, MALT1-nearby variant rs2874116, MC4R-nearby variant rs1942872, PHLPP rs9958800 and DSEL-nearby variant rs9966483 single nucleotide polymorphisms (SNPs) in the 18q region, previously linked with DN in African-Americans, with T2DM in (North African) Tunisian subjects, followed by their association with DN, which was performed subsequent to the analysis of the association with T2DM. Study subjects comprised 900 T2DM cases and 748 normoglycemic control, and genotyping was carried out by PCR-RFLP analysis. Of the 5 SNPs analyzed, POL1-nearby variant rs488846 [P= 0.044], and MC4R-nearby variant rs1942872 [P= 0.012] were associated with moderate risk of T2DM. However, there was a lack of consistency in the association of the 5 tested SNPs with DN. As such, it appears that the three chromosome 18q region variants appear to play a role in T2DM pathogenesis, but not with DN in North African Tunisian Arabs. © 2013 Elsevier B.V. Source

Turki A.,University of Monastir | Mtiraoui N.,University of Monastir | Al-Busaidi A.S.,Arabian Gulf University | Khirallah M.,CHU Fattouma Bourguiba | And 2 more authors.
Diabetes Research and Clinical Practice | Year: 2012

Aims: Polymorphisms of KCNQ1 were previously associated with type 2 diabetes (T2DM) in select Caucasian and non-Caucasian populations. We investigated the association of rs231361, rs231359, rs151290, rs2237892, rs2283228, rs2237895, and rs2237896 KCNQ1 polymorphisms with T2DM in Tunisian Arabs. Subjects and methods: Subjects comprised 900 T2DM patients and 600 normoglycemic controls. KCNQ1 genotyping was done by allelic discrimination (real-time PCR) and PCR-RFLP methods; the contribution of KCNQ1 polymorphisms to T2DM were analyzed by Haploview and regression analysis. Results: Minor allele frequency (MAF) of the 7 tested KCNQ1 variants was comparable between T2DM cases and controls. Mild association of rs2237892 genotypes with T2DM was seen (P=. 0.014), highlighted by the significant association of the C/T genotype with increased T2DM risk (OR, 2.11; 95%CI, 1.25-3.53), after adjusting for BMI, gender, systolic and diastolic blood pressure, and serum lipid profile. Heterogeneity in linkage disequilibrium pattern between tested KCNQ1 variants analyzed was seen. Two-locus (rs231361 and rs231359) and 5-locus (remaining 5 SNPs) haplotype analysis did not reveal any significant association with any of the haplotypes contained in either block 1 or block 2. Conclusion: These results indicate that there was no evidence for an association of KCNQ1 polymorphisms with T2DM in Tunisian Arabs. © 2012 Elsevier Ireland Ltd. Source

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