New Insight into the human genetic diversity in North African populations by genotyping of SNPs in DRD3, CSMD1 and NRG1 genes.

BACKGROUND: The single nucleotide polymorphisms (SNPs) of the dopamine D3 receptor (DRD3), the CUB and sushi multiple domains 1 (CSMD1) and the neuregulin 1 (NRG1) genes were used to study the genetic diversity and affinity among North African populations and to examine their genetic relationships in worldwide populations. METHODS: The rs3773678, rs3732783 and rs6280 SNPs of the DRD3 gene located on chromosome 3, the rs10108270 SNP of the CSMD1 gene and the rs383632, rs385396 and rs1462906 SNPs of the NRG1 gene located on chromosome 8 were analysed in 366 individuals from seven North African populations (Libya, Kairouan, Mehdia, Sousse, Kesra, Smar and Kerkennah). RESULTS: The low values of FST indicated that only 0.27%-1.65% of the genetic variability was due to the differences between the populations. The Kairouan population has the lowest average heterozygosity among the North African populations. Haplotypes composed of the ancestral alleles ACC and ACAT were more frequent in the Kairouan population than in other North African populations. The PCA and the haplotypic analysis showed that the genetic structure of populations in North Africa was closer to that of Europeans, Admixed Americans, South Asians and East Asians. However, analysis of the rs3732783 and rs6280 SNPs revealed that the CT microhaplotype was specific to the North African population. CONCLUSIONS: The Kairouan population exhibited a relatively low rate of genetic variability. The North African population has undergone significant gene flow but also evolutionary forces that have made it genetically distinct from other populations.

Akt activation correlates with the tumor aggressiveness in Tunisian patients with bladder cancer.

Various studies in western countries found Akt amplification to be a frequent event in human cancers, including bladder, but the correlation with clinicopathological features is controversial. Such studies have not been reported in African populations, including Tunisians. The purpose of this study was to assess expression of the phosphorylated/activated forms of Akt in tumors from Tunisian patients with bladder cancer and to correlate its expression with pathological and clinical parameters of the disease. The study included 72 patients of whom 34 were diagnosed as low- to medium-grade and 35 as high-grade; 30 were muscle stage and 39 non-muscle stage. Primary tumors from these patients, normal adjacent tissues, or bladder cancer cell-lines were analyzed for Ser473 phosphorylated Akt expression by Western blot. Seventy-two percent of primary tumors from patients with bladder cancer had increased levels of p-Akt. The p-Akt levels in patients with high-grade bladder cancer were significantly elevated compared to patients with low- or medium-grade bladder cancer. In invasive carcinoma, the p-Akt level was significantly higher than in superficial non-invasive bladder tumors. Concerning the influence of tobacco on Akt activation, no significant differences of p-Akt expression were found between non-smoker and smoker patients. Altogether, our results suggest that Akt activation can provide useful prognostic information and that tobacco represents a serious risk factor for recurrence in a cohort of Tunisian patients.

Assessment of Aurora A kinase expression in breast cancer: a tool for early diagnosis?

Aurora A kinase is overexpressed in many cancers but the status of this protein in the breast cancer often varies. We investigate the expression and localization of Aurora A protein in relation with tumor emergence and progression in breast cancer. Aurora A kinase status was evaluated in 107 patients using immunohistochemistry. The experimental findings showed that high expression of the Aurora A protein was correlated with elevated nuclear grade, low expression of progesterone receptor and positive nodal status. The experimental results showed also that the localization of this kinase shifts from cytoplasm in non malignant adjacent tissue to both cytoplasmic and nuclear compartments in tumoral tissue, suggesting an oncogenic role of the nuclear accumulation. We have, furthermore, detected the overexpression of this protein in non malignant adjacent tissue. The expression of the Aurora A kinase in non malignant tissue may represent an earlier diagnosis tool for breast cancer.

Association analysis of LCE3C-LCE3B deletion in Tunisian psoriatic population.

An association between a common deletion comprising the late cornified envelope LCE3B and LCE3C genes (LCE3C_LCE3B-del) and psoriasis has been reported in Caucasian and Asian populations. To investigate whether this deletion plays a role in the genetic of psoriasis in Tunisian population, we determined the LCE3C_LCE3B-del genotype in 180 Ps patients and 208 healthy controls from different regions of Tunisia. The LCE3B and LCE3C gene variant was determined in the patients through PCR amplification and the SPSS software package. The frequency of the LCE3C_LCE3B-del was similar between patients and healthy controls. Subanalyses by family history revealed that the frequency of LCE3C_LCE3B-del was significantly higher in patients with a positive family history than in control individuals, as well as in individuals with a positive family history versus those without in the case cohort. However, no significant difference was observed between psoriatic patients with no family history and controls. We also evaluated the relationship between LCE3C_LCE3B-del and PSORS1. No significant epistatic effect was observed suggesting that there was no significant epistasis of the two loci in the Tunisian population. Our findings indicate that the LCE3C_LCE3B-del might play a role in familial psoriasis in the Tunisian population.

[Immunogenetics of psoriasis: update]. / Immunogénétique du psoriasis : actualités.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease often benign, affecting 2-3% of the total world population. Psoriasis is a multifactorial disease. AIM: To present recent advances in the immunologic mechanisms and susceptibility genes involved in the pathogenesis of psoriasis. METHODS: We presented a literature review of recent genetic and immunological basis of psoriasis to better understand the pathomecanisms of this disease and discuss the contribution of the Tunisian work in this area. RESULTS: Recent works focalized mainly in immunology and genetics. Current progresses in molecular biology have allowed to better characterize the immunogenetic abnormalities in psoriasis. CONCLUSION: Psoriasis is a multifactorial disease model in which environmental factors (psychological, climate, traumatic, infectious, and viral) seem to be triggering factors when associated with a particular immunogenetics predisposition.

[Penetrance of BRCA1 gene mutation and DNA mitochondrial in Tunisian breast cancer occurrence]. / Pénétrance des mutations du gène BRCA1 et de l'ADN mitochondrial dans l'occurrence du cancer du sein en Tunisie.

AIM: The aim of this study is to evaluate the implication of BRCA1 gene and the mitochondrial micro satellite (situated between 303 and 315 positions) mutations in the occurrence of breast cancer in Tunisia. METHODS: Nine Tunisian patients with hereditary breast cancer have been analyzed. For each patient, total genomic DNA was extracted and used as a template for the amplification of 24 exons of the BRCA1 gene and an hyper variable mitochondrial region. The obtained products were purified and automatically sequenced. RESULTS: The results revealed five types of mutations for the micro satellite situated between the 303 and 315 positions and two deleterious BRCA1 mutations for two unrelated patients which present the same mitochondrial mutation (315.insC) suggesting his implication in the modulation of the BRCA1 deleterious mutations penetrance.