A3243G mitochondrial DNA mutation in Tunisian diabetic population.

BACKGROUND: An excess of maternal transmission of adult onset diabetes mellitus has been observed in the studied Tunisian patients, in fact, diabetic patients with affected mother are significantly more important than those with affected father (p< 10-6) There is increasing evidence that mtDNA mutations may be involved in this disease, since mitochondrial transmission offers a plausible explanation for a proportion of this maternal excess comparing to paternal transmission. AIM: The aim of the present study was to investigate the mitochondrial DNA involvement in the inheritance of diabetes in Tunisian population and to evaluate the frequency of substitution A3243G in these patients. METHODS: In the current study we investigated for the first time, the 3243 mtDNA in 280 Tunisian diabetic patients. RESULTS: Results showed that the frequency of this substitution in tRNALeu is about 1.07%. This percentage is similar to those reported in Japanese, German and French populations.

Mitochondrial DNA haplogroup H structure in North Africa.

BACKGROUND: The Strait of Gibraltar separating the Iberian Peninsula from North Africa is thought to be a stronger barrier to gene flow for male than for female lineages. However, the recent subdivision of the haplogroup H at mitochondrial DNA (mtDNA) level has revealed greater genetic differentiation among geographic regions than previously detected. The dissection of the mtDNA haplogroup H in North Africa, and its comparison with the Iberian Peninsula and Near-East profiles would help clarify the relative affinities among these regions. RESULTS: Like the Iberian Peninsula, the dominant mtDNA haplogroup H subgroups in North Africa are H1 (42%) and H3 (13%). The similarity between these regions is stronger in the North-West edge affecting mainly Moroccan Arabs, West Saharans and Mauritanians, and decreases eastwards probably due to gene flow from Near East as attested for the higher frequencies of H4, H5, H7, H8 and H11 subgroups. Moroccan Berbers show stronger affinities with Tunisian and Tunisian Berbers than with Moroccan Arabs. Coalescence ages for H1 (11 +/- 2 ky) and H3 (11 +/- 4 ky) in North Africa point to the possibility of a late Palaeolithic settlement for these lineages similar to those found for other mtDNA haplogroups. Total and partial mtDNA genomic sequencing unveiled stronger mtDNA differentiation among regions than previously found using HVSI mtDNA based analysis. CONCLUSION: The subdivision of the mtDNA haplogroup H in North Africa has confirmed that the genetic differentiation found among Western and Eastern populations is mainly due to geographical rather than cultural barriers. It also shows that the historical Arabian role on the region had more a cultural than a demic effect. Whole mtDNA sequencing of identical H haplotypes based on HVSI and RFLP information has unveiled additional mtDNA differences between North African and Iberian Peninsula lineages, pointing to an older mtDNA genetic flow between regions than previously thought. Based on this new information, it seems that the Strait of Gibraltar barrier affected both male and female gene flow in a similar fashion.

Association of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene with type 2 diabetes in two ethnic groups of Jerba Island in Tunisia.

INTRODUCTION: The aim of the current study was to evaluate the role of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism on the prediction of type 2 diabetes in two ethnic populations from Jerba Island,Tunisia. METHODS: In this study, we analysed the genotypic and the allelic distributions of the ACE I/D polymorphism and conducted a case/control association study between healthy normoglycaemic controls and diabetic patients in the two studied groups.ACE gene polymorphism was analysed by polymerase chain reaction in 272 individuals consisting of 172 diabetic subjects and 100 controls. RESULTS: The genotype frequencies for DD, ID and II were 75.50%, 19.60% and 4.89% inArabs and 76.66%, 16.66% and 6.67% in Berbers, respectively, in the case group, and 42.85%, 35.71% and 21.43% inArabs and 57.50%, 22.50% and 20.00% in Berbers, respectively, in the control group.The DD frequency was significantly higher in the case group than in the control group (p<0.001), suggesting that the DD genotype is associated with an increased susceptibility to type 2 diabetes in our study populations. CONCLUSIONS: The current investigation provides new evidence regarding the role of the ACE I/D polymorphism in the pathogenesis of type 2 diabetes in Jerbian populations. Furthermore, it underlines the importance of ethnicity, which should be considered in all studies aiming to test the genetic effects on the susceptibility to type 2 diabetes.

Computer-Assisted Classification Patterns in Autoimmune Diagnostics: The AIDA Project.

Antinuclear antibodies (ANAs) are significant biomarkers in the diagnosis of autoimmune diseases in humans, done by mean of Indirect ImmunoFluorescence (IIF) method, and performed by analyzing patterns and fluorescence intensity. This paper introduces the AIDA Project (autoimmunity: diagnosis assisted by computer) developed in the framework of an Italy-Tunisia cross-border cooperation and its preliminary results. A database of interpreted IIF images is being collected through the exchange of images and double reporting and a Gold Standard database, containing around 1000 double reported images, has been settled. The Gold Standard database is used for optimization of a CAD (Computer Aided Detection) solution and for the assessment of its added value, in order to be applied along with an Immunologist as a second Reader in detection of autoantibodies. This CAD system is able to identify on IIF images the fluorescence intensity and the fluorescence pattern. Preliminary results show that CAD, used as second Reader, appeared to perform better than Junior Immunologists and hence may significantly improve their efficacy; compared with two Junior Immunologists, the CAD system showed higher Intensity Accuracy (85,5% versus 66,0% and 66,0%), higher Patterns Accuracy (79,3% versus 48,0% and 66,2%), and higher Mean Class Accuracy (79,4% versus 56,7% and 64.2%).

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.

Study of TNFalpha -308G/A and IL6 -174G/C polymorphisms in type 2 diabetes and obesity risk in the Tunisian population.

OBJECTIVES: We investigated two genetic markers in pro inflammatory molecules : TNFalpha -308G/A and IL6 -174G/C in order to assess their effect on type 2 diabetes (T2D) and obesity in the Tunisian population. DESIGN AND METHODS: The study sample includes 228 patients with T2D and 300 healthy controls. Genotyping of IL6 -174G/C (rs1800795) was performed using Automated Dye Terminator Sequencing and of TNFalpha -308G/A (rs1800629) using the LightTyper technology. RESULTS: SNPs IL6 -174G/C and TNFalpha -308G/A are associated neither with T2D (p=0.89, p=0.34 respectively) nor with risk for overweight (p=0.86, p=0.12 respectively) in Tunisian population. Bonferroni correction showed that the founded association of IL6 -174G/C SNP with T2D susceptibility restricted to overweight patients (p(nominal)=0.03, p(corrected)=0.0033) is likely to be a random result. CONCLUSION: SNPs IL6 -174G/C and TNFalpha -308G/A are not major contributors to T2D or obesity risk in our Tunisian population.

The role of CYP2D6*4 variant in bladder cancer susceptibility in Tunisian patients.

CYP2D6 enzyme is implicated in the metabolism of drugs and nicotine. Genetic variability within CYP2D6, results in different CYP2D6 phenotypes. Inheritance of polymorphic CYP2D6 metabolizing enzyme is likely to be an important determinant of inter-individual variations in susceptibility to cancer. In this work, we have conducted a case control study in order to assess the role of CYP2D6*4 variant in bladder cancer development in a Tunisian cohort. A total of 80 patients with TCC of bladder cancer and 109 healthy controls were included in the present study. The frequency of CYP2D6*4 allele, characterized by loss of BstNI site, was observed in 8.25% of healthy volunteers and in 10.62% of patients. The CYP2D6*4/CYP2D6*4 genotype was observed in only 2.75% of controls and was absent in cases. In all group of patients, the CYP2D6*4 allele did not appear to influence bladder cancer susceptibility (p > 0.05). A similar result was obtained when we stratified cases group according to tobacco status. Conversely, patients carrying the BstNI site at the homozygous state, mostly combined as homozygous wild genotype, could be at more risk of bladder cancer invasiveness than those having the heterozygous genotype.