Thymidylate synthase polymorphism in sporadic colorectal and gastric cancer in Tunisian population: a predictive role in 5-fluorouracil based chemotherapy treatment.

In our study, we investigate the possible association of thymidylate synthase polymorphism, 28 bp tandem repeat in 5'-UTR (transcription enhancer element) with susceptibility of colorectal and gastric cancer in Tunisian population. Because thymidylate synthase provides an effective prediction of chemotherapy treatment based on 5-fluorouracil, our interest in this study was focused on finding an eventual interaction between thymidylate synthase polymorphism and treatment of sporadic colorectal and gastric cancer. Whole blood was collected into EDTA tube, after centrifugation for 15 min, the buffy coat was isolated, and genotyping of TS 5'-UTR polymorphism was carried by polymerase chain reaction method using appropriate primers. Determination of the different genotypes was done directly on the stained agarose gel. Our finding showed that the 5'tandem repeat polymorphism of the thymidylate synthase gene is associated with risk of colorectal cancer; thus, LL (3R/3R) genotype is significantly high in patients with colorectal cancer compared to controls (P = 0.002; OR 2.7; 95 % CI 1.4-5.2). In addition, we found a positive association between SL (2R/3R) genotype in the thymidylate synthase 5'-UTR and gastric cancer risk (P = 0.015; OR 4.46; 95 % CI 1.08-19.64). Furthermore, we found a correlation of thymidylate synthase polymorphism with the fluorouracil-based therapy regimes and also with preoperatory radiation in patients with colorectal cancer. Thymidylate synthase is associated with risk of colorectal cancer but not with gastric cancer; however, heterozygous SL (2R/3R) polymorphism is associated with risk of gastric cancer; moreover, the 5' tandem repeat polymorphism of thymidylate synthase gene was an independent predictor of the clinical treatment.

Genetic susceptibility to type 2 diabetes: a global meta-analysis studying the genetic differences in Tunisian populations.

The present study is the first meta-analysis to evaluate type 2 diabetes (T2D)- associated polymorphisms in cohorts originated from several Tunisian regions. In fact, we evaluated the effect of seven polymorphisms in the following genes-PPARg (Pro12Ala), TNFα (-308A/G), ENPP1(K121Q), TCF7L2(rs7903146°C/T), MTHFR(C677T), ACE(I/D), and CAPN10(3R/2R)-on T2D risk, through a meta-analysis combining data of previous studies performed on Tunisian populations originating from the north, center, or south of the country. R statistics version 2.12.1 software was used to estimate the heterogeneity between studies. Pooled odds ratios were computed by the fixed-effects method of Mantel-Haenszel if no heterogeneity between studies exists. Despite the similarities founded in a number of loci, the Woolf test reported that the contributions of ENPP1 and ACE loci in T2D risk are dependent on the geographic origin of concerned groups, and this heterogeneity could be attributed not only to the variable contribution of the variant in T2D risk but also to diversities of genetic background between tested groups. Interestingly, observed heterogeneity highlighted founding concerning Y chromosome and the mitochondrial DNA about the genetic structure of Tunisian population and proves once again that Tunisians, like the north-Africans, are a mosaic of subpopulations, with significant differences in genetic structure. In homogeneous groups, we replicated the association of single-nucleotide polymorphisms of TCF7L2, MTHFR, CAPN 10, TNFα, and ACE genes with a T2D risk in the Tunisian population with OR ranging from 1.43 to 6.72. However, we reported an absence of the association of PPARg with T2D 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.

Dietary intakes of essential nutrients among Arab and Berber ethnic groups on rural Tunisian island.

OBJECTIVE: The dietary intake was investigated and food sources were identified among Tunisian ethnic groups from Jerba Island in the south of Tunisia. METHODS: Ninety-four subjects of moderate socioeconomic status (47 Berbers and 47 Arabs) aged 32 to 64 y completed a 1-mo qualitative food-frequency questionnaire and a single 24-h dietary recall, and dietary intakes and demographic status were observed from 2006 to 2007. RESULTS: The prevalence of overweight and obesity was not significantly associated with Arab men compared with Berber men. Therefore, obesity was significantly associated with Berber women (P<0.001). Height was significantly different between Arab and Berber women (P<0.001). There were no significant differences in energy intake between men and women. Protein intake was not significantly different between ethnic groups. Milk and dairy products in the Berber group were significantly different from the Arab group. Intakes of calcium, zinc, iron, and folate were below recommended nutrient intakes in men and women in the two ethnic groups. Vitamin E intake was greater in Berbers than in Arabs (P<0.01). CONCLUSION: Ethnicity was significantly associated with dietary intakes in the two ethnic groups of Jerba Island.

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.