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Mtiraoui N.,University of Monastir | Ezzidi I.,University of Monastir | Turki A.,University of Monastir | Chaieb M.,CHU Farhat Hached of Sousse | And 2 more authors.
JRAAS - Journal of the Renin-Angiotensin-Aldosterone System | Year: 2011

Background: The association between renin C-4063T and angiotensinogen (AGT) T174M, M235T, and A-6G polymorphisms with diabetic nephropathy (DN) was investigated in Tunisian type 2 diabetes (T2DM) patients.Methods: Study subjects comprised 917 T2DM patients (405 normoalbuminuric, 329 microalbuminuric and 185 macroalbuminuric). Genotyping was done by PCR-RFLP.Results: Renin C-4063T allele and genotype frequencies were comparable between DN cases and normoalbuminuric controls. Although AGT 235T and -6G allele, and 235T/T and -6G/G genotype frequencies were higher in DN compared to normoalbuminuric patients, they were comparable between microalbuminuric or macroalbuminuric patients. Three-locus AGT haplotype analysis (A-6G/T174M/M235T) identified DN-protective (ATM, AMM, GTM) and DN-susceptible (GTM, ATT, GMT and AMT) haplotypes, and demonstrated enrichment of GTT haplotype in macroalbuminuric compared to microalbuminuric or normoalbuminuric patients. Regression analysis confirmed negative (AMM) and positive (GTM, ATT, GMT, AMT) association of AGT haplotypes with microalbuminuria, and negative (AMM) and positive (GTM and ATT) association of AGT haplotypes with macroalbuminuria. None of the AGT haplotypes was associated with DN severity.Conclusions: Genetic variation at the AGT gene influences the risk of nephropathy in T2DM patients but not extent of DN severity, and thus represents a potential DN genetic susceptibility locus worthy of replication. © SAGE Publications 2011. Source


Ziadi S.,CHU Farhat Hached of Sousse | Ksiaa F.,CHU Farhat Hached of Sousse | Gacem R.B.,CHU Farhat Hached of Sousse | Labaied N.,CHU Farhat Hached of Sousse | And 2 more authors.
Pathology Research and Practice | Year: 2014

Colorectal cancer (CRC) can be classified according to the level of microsatellite instability (MSI) exhibited by the tumor. The aim of this study was to determine MSI status in CRC from Tunisia and to identify clinical and pathological characteristics of MSI-H tumors.Microsatellite status was determined by polymerase chain reaction amplification using standard markers (BAT25, BAT26, D2S123, D5S346 and D17S250, the Bethesda panel) in 44 CRC cases. Molecular results were correlated with pathological and clinical features.Six CRC cases (13.8%) showed high-level instability (MSI-H), 14 cases had low level instability (MSI-L), and the remainders were stable (MSS). Immunohistochemical analysis showed loss of MSH2 protein in 3 cases among the 6 MSI-H tumors, whereas no silencing of MLH1 or MSH6 was found in any case. Significant differences in age and family history of cancers were observed between MSI-H and MSS/MSI-L groups ( p= 0.01 and p= 0.002). However, statistical analysis showed that there were no significant differences between MSI-H and MSS/MSI-L tumors in terms of tumor location, lymph node involvement and stage of disease. Regarding histological features, MSI-H tumors were more likely to be poorly differentiated ( p= 0.003), to have a medullary pattern ( p= 0.005), and to harbor increased numbers of peritumoral lymphocytes ( p= 0.001).These findings indicate that careful observation of the tumor morphology can assist in the identification of unstable colorectal cancers requiring molecular investigations. © 2013 Elsevier GmbH. Source

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