The 72Pro Variant of the Tumor Protein 53 Is Associated with an Increased Breast Cancer Risk in the Moroccan Population.

BACKGROUND: The purpose of our case control study is to explore the potential association of tumor protein 53 (TP53) c.215G>C, p. (Arg72Pro) polymorphism (rs1042522) with the risk of breast cancer (BC) development in the Moroccan population. METHODS AND RESULTS: The study population consisted of 125 female patients with confirmed BC and 126 healthy controls. DNA samples were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism assay method using BstUI restriction enzyme. We showed that the homozygous genotype of TP53 72Pro variant was significantly associated with increased BC risk (OR 2.2, 95% CI 1.07-4.54, p = 0.03). The dominant and additive models of TP53 Pro allele were also correlated to the risk of BC (OR 2.13, 95% CI 1.07-4.23, p = 0.02 and OR 1.49, 95% CI 1.03-2.16, p = 0.03, respectively). Furthermore, the TP53 Arg72 variant was associated with protection against BC, either in the homozygous genotype, the dominant or the additive models (OR 0.45, 95% CI 0.22-0.93, p = 0.03; OR 0.46, 95% CI 0.23-0.92, p = 0.029 and OR 0.67, 95% CI 0.46-0.97, p = 0.03, respectively). CONCLUSION: Our results suggest that TP53 c.215G>C, p. (Arg72Pro) polymorphism may be considered as a genetic marker for predisposition to BC in Moroccan population.

Anti-inflammatory potential of Capparis spinosa L. in vivo in mice through inhibition of cell infiltration and cytokine gene expression.

BACKGROUND: Several chronic inflammatory diseases are characterized by inappropriate CD4+ T cell response. In the present study, we assessed the ability of Capparis spinosa L. (CS) preparation to orientate, in vivo, the immune response mediated by CD4+ T cells towards an anti-inflammatory response. METHODS: The in vivo study was carried out by using the contact hypersensitivity (CHS) model in Swiss mice. Then we performed a histological analysis followed by molecular study by using real time RT-PCR. We also realized a phytochemical screening and a liquid-liquid separation of CS preparation. RESULTS: Our study allowed us to detect a significantly reduced edema in mice treated with CS preparations relative to control. CS effect was dose dependent, statistically similar to that observed with indomethacin, independent of the plant genotype and of the period of treatment. Furthermore, our histology studies revealed that CS induced a significant decrease in immune cell infiltration, in vasodilatation and in dermis thickness in the inflammatory site. Interestingly, we showed that CS operated by inhibiting cytokine gene expression including IFNγ, IL-17 and IL-4. Besides, phytochemical screening of CS extract showed the presence of several chemical families such as saponins, flavonoids and alkaloids. One (hexane fraction) out of the three distinct prepared fractions, exhibited an anti-inflammatory effect similar to that of the raw preparation, and would likely contain the bioactive(s) molecule(s). CONCLUSIONS: Altogether, our data indicate that CS regulates inflammation induced in vivo in mice and thus could be a source of anti-inflammatory molecules, which could be used in some T lymphocyte-dependent inflammatory diseases.

Assessment of GAPDH expression by quantitative real time PCR in blood of Moroccan AD cases.

INTRODUCTION: Neuroproteomics studies have showed the high affinity interactions between GAPDH - ß-amyloid in Alzheimer disease. The aim of our study is to complete our previous studies by assessing the mechanism responsible of decreased expression of GAPDH protein in the blood of Moroccan AD cases probably due to an alteration at the transcriptional level or at the post translational level. METHODS: The mRNA expression of GAPDH was assessed by quantitative real time PCR in AD cases and healthy controls. RESULTS: Our result revealed a significant difference of mRNA expression level of GAPDH in AD cases as compared to healthy controls (P<0.05). CONCLUSION: This data is consistent with several studies by showing the direct involvement of GAPDH in amyloid aggregation by undergoing several modifications, which influence its chemical structure and its biological activity.

Screening of exon 11 of BRCA1 gene using the high resolution melting approach for diagnosis in Moroccan breast cancer patients.

BACKGROUND: Identification of specific mutations in cancer patients may lead to the discovery of genes, which can affect susceptibility and/or prognosis. It has previously been reported that mutations in BRCA1 and BRCA2 genes are linked to breast cancer. Here, we evaluated the use of the High Resolution Melting (HRM) approach to screen for mutations in exon 11 of BRCA1 gene in Moroccan patients. METHODS: HRM analysis was used to screen exon 11 from 71 breast cancer patients in order to detect different variants. Conventional Sanger sequencing was used to confirm the presence of possible mutations. Distribution of different SNPs was determined by SNaPshot analysis software. RESULTS: In order to assess the efficacy of the HRM approach to screen for mutations, especially in diagnosis, we first used two samples with previously known mutations, "2924delA and 3398delC". Indeed, these previously known sequence variants were detected by the HRM approach and yielded melting curves with atypical shape relative to wild-type control sequences. We then analyzed, 69 samples from breast cancer patients using the HRM method, and were able to detect two samples with atypical curves. Sequencing of the two samples, using the conventional Sanger approach, confirmed the presence of the same SNP (c.2612C > T) in both samples. CONCLUSIONS: Our results strongly suggest that the HRM approach represents a reliable and highly sensitive method for mutation scanning, especially in diagnosis.