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This study aimed to investigate whether plasma 25-hydroxyvitamin D (25-OHD) at diagnosis predicts poor outcomes in patients with urothelial bladder cancer. A total of 177 patients with non-muscle-invasive bladder cancer (NMIBC) were prospectively followed up over a period extending beyond 6 years. Data on poor outcomes (ie., recurrence, progression, and mortality) were collected. Plasma 25-OHD was measured by immunoassay. Cutoff-Finder web application was used to determine the best 25-OHD cutoff point to predict a specific poor outcome. Cox-hazard models were applied to test how plasma 25-OHD affect patients outcome while adjusting for potential confounding factors. During the follow-up period, tumor recurrence and progression occurred in 40.7% and 14.1% of patients, respectively and 11.3% of patients died. Baseline 25-OHD was lower in patients who experienced poor outcome (12.2 ± 7.44

Behçet's disease (BD) is a multisystem inflammatory disease of unknown etiology. Beta-defensins are antimicrobial peptides involved in epithelial host defense. To explore whether beta-defensins might be involved in BD pathogenesis, we examined plasma human beta-defensin-1 (hBD-1) and DEFB1 -20G/A polymorphism in BD patients.This case-control study included 106 BD patients fulfilling the criteria of the International Study Group for BD and 156 controls. The -20G/A genotypes were determined by PCR-RFLP analysis in all participants, and plasma hBD-1 was assessed by ELISA in 77 BD patients and 44 controls, only. Stepwise multiple regression models were applied to determine independent predictors for plasma hBD-1 in BD patients.Distribution of -20G/A genotypes was different between BD patients and controls. Compared to GG genotype, "GA" genotype [OR (95% CI), 3.12 (1.56-6.16); p = .001] and "AA" genotype [2.57 (1.10-5.96); p = .027)] were associated with increased risk for BD. Plasma hBD-1 concentrations were significantly higher in BD patients than controls (9.81 ± 3.52 ng/mL vs. 5.30 ± 3.02 ng/mL; p .001), and in BD patients with neurological involvement than those without (11.1 ± 4.12 ng/mL vs. 9.19 ± 3.10 ng/mL; p = .040). No variation was noted according to other clinical features, treatment received or -20G/A genotypes. In multivariate analysis, neurological involvement was the only predictor for plasma hBD-1 (β, 0.274; p = .029).Findings suggest that hBD-1 and its encoding gene DEFB1 could modulate the risk for BD, especially for BD neurological involvement. Further work is needed for a better understanding of role of hBD-1 and its genetic variants in the pathogenesis of BD.

Purpose: In this study, we investigated the association of two polymorphisms (rs869109213 and rs2070744) in the eNOS gene and one polymorphism BglII in the α2β1 integrin gene (ITGA2) with the risk ...

Inflammation is a marker of arterial disease stemming from cholesterol-dependent to -independent molecular mechanisms. In recent years, the role of inflammation in atherogenesis has been underpinned by pharmacological approaches targeting systemic inflammation that have led to a significant reduction in cardiovascular disease (CVD) risk. Although the use of nutraceuticals to prevent CVD has largely focused on lipid-lowering (e.g, red-yeast rice and omega-3 fatty acids), there is growing interest and need, especially now in the time of coronavirus pandemic, in the use of nutraceuticals to reduce inflammatory markers, and potentially the inflammatory CVD burden, however, there is still not enough evidence to confirm this. Indeed, diet is an important lifestyle determinant of health and can influence both systemic and vascular inflammation, to varying extents, according to the individual nutraceutical constituents. Thus, the aim of this Position Paper is to provide the first attempt at recommendations on the use of nutraceuticals with effective anti-inflammatory properties.

The study aimed to examine circulating vitamins A, E, D, and B12 and folate in patients with urothelial bladder cancer (UBC) and detect potential interaction effects of these micronutrients on UBC risk. A case-control study was conducted on 262 UBC patients and 254 matched controls. Vitamins A and E were assessed by ultra performance liquid chromatography, and vitamins D and B12 and folate were assessed by immunological methods. Binary logistic regression models were used to test associations of plasma vitamins tertiles with UBC risk. A multifactor dimensionality reduction method (MDR) was applied to assess interactive effects of the vitamins and tobacco on UBC risk. Higher levels in vitamins A, E, and D were associated with lower occurrence of UBC. No significant association was observed in plasma folate or vitamin B12 with UBC. There were redundancy interactions of plasma vitamin D with tobacco and with plasma vitamin A on UBC risk. Even though the study could not ascertain causality, the findings suggest that vitamins A, E, and D might be protective against UBC. Vitamins A and D interact antagonistically with each other's and with tobacco to modulate UBC risk. These interactions should be taken in consideration for the prevention of UBC.

Fatty acids (FAs) are thought to impact carcinogenesis by affecting cell signaling. A case-control study including 250 patients with urothelial bladder cancer (UBC) and 250 controls was conducted. Plasma FAs composition was assessed using capillary gas chromatography. Associations of individual and classes of FAs with UBC were controlled for the main risk factors for UBC. Plasma FAs profile was different in patients compared to controls. Higher levels (third tertile vs. first tertile) in palmitic acid (PA) [multi-adjusted OR (95% CI), 1.83 (1.14-2.92)], and n - 6:n - 3 FA ratio [4.13 (2.38-7.16)] were associated with increased risk for UBC [multi-adjusted OR (95% CI), 1.83 (1.14-2.92)]. In contrast, higher levels (third tertile vs. first tertile) in oleic [0.54 (0.34-0.86)], dihomo-γ-linolenic (DGLA) [0.47 (0.29-0.74)], eicosapentaenoic (EPA) [0.32 (0.19-0.52)], and docosahexaenoic (DHA) acids [0.33 (0.20-0.53)] were associated with lower risk for UBC. Although the study design does not allow proving causality, the findings suggest a possible protective role of oleic acid and marine n - 3 polyunsaturated FAs (PUFAs) against bladder carcinogenesis.

Objective: This study aims to investigate the association of 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and methionine synthase reductase (MTRR A66G) gene polymorphisms with neural tube defects (NTDs) in a Tunisian population. Methods: Genotyping was performed by polymerase chain reaction with restriction fragment length polymorphisms (PCR-RFLPs) using the restriction enzymes. Allele and genotype frequencies were compared between mothers and fathers of fetuses with NTDs with matched controls based on an association analysis using SPSS software. Results: MTHFR (C677T, A1298C) and MTRR A66G polymorphisms were found to be protector factors for NTD fetuses in the mother group. In addition, a combination of the three wild-type alleles C677/A1298/A66 has increased four-fold the incidence of NTDs (p = 0.004, OR = 3.96, 95% CI: 1.53–10.23). In the father group, MTHFR C677T was a risk factor for NTDs. However, no association was found between MTHFR A1298C, MTRR A66G, and the occurrence of this anomaly. The analysis of MTHFR C677T and MTRR A66G polymorphisms has demonstrated a significant difference in vitamin B12 levels between recessive and dominant genotypes in case mothers (p < 0.05). Conclusion: Additional studies are required to better understand the roles of parental gene polymorphisms related to folate-homocysteine metabolism in the pathogenesis of NTD.

BACKGROUND/AIM: Accumulated data suggested that Vascular Endothelial Growth Factor is a major mediator in vasculogenesis, angiogenesis and recently in tumorigenesis. Therefore, we aimed to investigate for the first time the association between VEGF gene variants (‐2549I/D (rs35569394), ‐2578C/A (rs699947), and +936C/T (rs3025039)) with urothelial bladder cancer (UBC) in Tunisian population. METHODS: A total of 218 UBC patients and 204 controls were recruited and genotyped by Polymerase Chain Reaction technique. Odds ratios (OR) and 95% confidence intervals (CIs) were used to access the association between the VEGFA gene polymorphisms and UBC. RESULTS: We found a significant decreased risk association of ‐2578 C/A polymorphism with UBC (OR (95% CI), 0.62 (0.41‐0.94), P = .026) for CA genotype and (OR (95% CI), 0.40 (0.21‐0.76), P = .005) for double homozygous mutant genotype. No associations were found in case of both polymorphic sites of VEGF, vis. ‐2549I/D and +936C/T, respectively. Haplotype analysis revealed a strong linkage disequilibrium between ‐2578C/A and ‐2549I/D and CIC combination is the significant haplotype associated with increased risk of UBC (OR (95% CI), 3.63 (1.47‐8.97), P = .005). Regarding tumor grade/stage and family history of cancer, no associations were found for ‐2578C/A polymorphism. CONCLUSION: CIC haplotype of VEGF gene may be important risk factor for UBC development in Tunisia.

Background Primary Sjogren syndrome (PSS) is one of the most common auto-immune systemic rheumatic diseases although its prevalence anging between 0.6 and 1.7%. PSS affects exocrine glands and lead to sicca syndrome. Interleukin-10 (IL-10) is a pleiotropic cytokine that is involved in the inflammation process of PSS. Objectives The aim of our study was to determine in a Tunisian population, clinical and biological characteristics of patients with primary PSS, allelic and genotypic frequencies of (-1082G/A, -819 C/T and -592 C/A) polymorphisms in IL-10 gene and to evaluate the association of these polymorphism with PSS. Methods The population we studied consisted of 242 subjects with female predominance (average age at diagnosis =49 years), divided into 84 PSS patients (fulfilling the revised AECG criteria 2002 and/or ACR proposed criteria 2012),recruited in the internal medicine department of the Rabta hospital and 158 controls recruited in the Greater Tunis. Il 10 level was assessed by ELISA. Polymorphisms genotyping of the IL-10 gene was done using PCR-RFLP technique. Results Il10 plasma level was lower in PSS patients (23.71pg/ml, n=73) compared to healthy volunteers (42.27pg/ml, n=60) and the difference was statistically significant (p=0.01). The genotype frequencies of our population respected Hardy-Weinberg equilibrium distribution both in patients by primary SS than in controls. In PSS patients, the genotype frequencies of -592C/A are 53% for the CC genotype, 41% for the CA and 6% for the AA genotype. In controls these frequencies are respectively 60.3%, 32.9% and 6.8%. The genotype frequencies of -1082 G/A are 29.6% for the AA genotype, 63% for the AG and 7.4% for the GG genotype. In controls these frequencies are respectively 41.5%, 52.1% and 6.3%. The genotype frequencies of -819 C/T are 47.6% for the CC genotype, 43.9% for the CT and 8.5% for the TT genotype. In controls these frequencies are respectively 41.5%, 52.1% and 6.3%. No significant differences in genotypic frequencies were observed between cases and controls in the three polymorphisms. Statistical analysis preformed revealed that there was neither protective nor aggravating hapoltype. However ATC haplotype seems to have a protective impact in controls (p=0.06 and OR=0.20) Conclusions IL10 level was significantly higher in PSS patients in precedent studies (1) (2). In our case Il10 level was associated with PSS in Tunisian patients but it was statistically lower than controls. Our results show that the three polymorphisms of gene of IL-10 are not a marker of SGS in the Tunisian population. This result might be explained by allelic variation or ethnic group. References Marka M, Bessenyei B, Zeher M, Semsei I. IL-10 promoter -1082 polymorphism is associated with elevated IL-10 levels in control subjects but does not explain elevated plasma IL-10 observed in Sjogren9s syndrome in a Hungarian cohort. Scandinavian journal of immunology. 2005;62(5):474–80. Vazquez-Villamar M, Palafox-Sanchez CA, Munoz-Valle JF, Valle Y, Orozco-Barocio G, Hernandez-Bello J, et al. Analysis of IL10 haplotypes in primary Sjogren9s syndrome patients from Western Mexico: Relationship with mRNA expression, IL-10 soluble levels, and autoantibodies. Human immunology. 2015;76(7):473–9. Disclosure of Interest None declared

Background Cluster of differentiation 40 (CD40), and its ligand CD40L, are major co-stimulatory molecules whose interactions are important in both cellular and humoral immunity, and has been suggested to play a role in the pathogenesis of acute coronary syndrome. Objective The aim of this study was to examine the association of CD40 polymorphisms (−1C > T (rs1883832) and 945G > T (rs4810485) and myocardial infarction (MI), and to test the association of CD40 gene haplotypes with MI in Tunisians. Materials and methods Three hundred and fifty MI patients and 301 apparently healthy controls were included in the study. The polymorphisms of CD40 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results A significant difference in genotype distribution and allele frequency was observed between patients and controls. The −1 C > T (rs1883832) polymorphism was associated with MI in co-dominant models (OR = 1.86; 95% CI: 1.15–3.03, P = 0.011) and recessive models (OR = 1.59; 95% CI: 1.01–2.05, P = 0.044). This association remained statistically significant after adjustment for age, diabetes, hypertension, dyslipidemia and smoking. Stratified analysis by gender showed that the CD40 −1C > T (rs1883832) polymorphism is associated with MI in males but not in females. In contrast, no significant difference in 945G > T (rs4810485) polymorphism genotype distribution and allele frequency was observed between patients and controls. Haplotypes analysis revealed that the C–T and T–G haplotypes were associated with an increased risk of MI with an odds ratio of 1.89, 95% CI: 1.14–3.14, P = 0.012 and 1.93, 95% CI: 1.37–2.71, P = Conclusion Our word showed a significant association between the −1 C > T (rs1883832) polymorphism of the CD40 gene and MI in the Tunisians.

Background Cardiovascular disease is the leading cause of death in Tunisia and worldwide. The incidence of cardiovascular diseases is directly proportional to that of the main atherosclerotic risk factors: arterial hypertension, diabetes mellitus, dyslipidemia, smoking and obesity. Up to day, in Tunisia there were no representative data on the adult prevalence rate. This is the reason behind starting a representative epidemiologic study to evaluate them and their evolution over time. Therefore the ATERA-Survey was initiated. Between January 2016 and February 2019, the Tunisian Association on Study and Research on Atherosclerosis (ATERA) and the International Atherosclerosis Society (IAS) made, for the first time, a large national study, the ATERA-Survey. Material and methods It is a cross-sectional, descriptive and analytical study of Tunisians aged 25 to 75 years living in the 24 governorates of Tunisia. A systematic and stratified random survey was conducted. Using a complex methodology and an innovative way of conducting a field survey, by the means of a medical caravan. Each subject answered the questionnaire on the nutritional state and cardiovascular risk factors, underwent a physical examination and had a blood sample drawn. Results The survey involved 11,955 individuals. The average age was 55 years. The prevalence of risk factors was: hypertension (50.5%), diabetes (18.2%), dyslipidemia (44%), obesity (body mass index ≥ 30 kgm2) (31.4%) and smoking (24.4%). Conclusion This survey found a high prevalence of cardiovascular risk factors in a general population in Tunisia. This should lead to better develop a strategy to prevent cardiovascular diseases.

Background & objectives: The impact of several environmental and genetic factors on diabetes is well documented. Though the association between the vitamin D receptor (VDR) gene polymorphisms and type 2 diabetes mellitus (T2DM) has been analyzed in different ethnic groups, the results have been inconsistent. The aim of this study was to evaluate the possible association between VDR FokI polymorphism and genetic susceptibility to T2DM in Tunisian population. Methods: A total of 439 unrelated patients with T2DM and 302 healthy controls were included in the study. Genomic DNA was extracted from blood and genotyped for the single nucleotide polymorphism (SNP) of FokI (T/C: (rs2228570) by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. Results: The genotype distribution and the relative allelic frequencies for the FokI polymorphism were not significantly different between T2DM and controls: in T2DM patients the frequencies of the CC, CT, and TT genotypes were 52.6, 41.0, and 6.1 per cent, respectively, and in controls the genotype frequencies were 55.6, 38.7, and 5.6 per cent, respectively. In our study, the TT genotype of the FokI polymorphism was not associated with T2DM (OR =1.19, 95% CI 0.63 - 2.25, P=0.577). Interpretation & conclusions: Our study showed no significant association of the FokI polymorphism in the vitamin D receptor gene with type 2 diabetes mellitus in Tunisian population.

BACKGROUND Adducin is a membrane cytoskeletal protein, consisting of three subunits: α, β, and γ subunits encoded by three different genes (ADD1, ADD2, ADD3). A specific mutation G460T of the α-adducin gene (ADD1) is associated with high renal tubular sodium reabsorption. This mutation is associated with salt sensitivity and may influence the risk of hypertension. In this study, we investigated the relationship between the G460T polymorphism of the ADD1 and essential hypertension (EH) in the Tunisian population. METHODS The case-controlled study included 280 patients with hypertension and 257 healthy controls. The G460T polymorphism of ADD1 was determined by polymerase chain reaction-restriction fragment length polymorphism analysis method. RESULTS In the whole population, the genotypic frequencies of the a-adducin G460T polymorphism in hypertensive and control groups (GG, GT, TT) were 78.6%, 17.5%, 3.9% and 87.5%, 11.29%, 1.16%, respectively (χ2 = 9.13, p < 0.01). The genotype was associated with hypertension, OR = 1.79, 95% CI (1.04 - 3.41), p < 0.03 for GT heterozygous and OR = 1.93, 95% CI (1.39 - 2.22), p < 0.03 for TT homozygous. Moreover, when we stratified the population according to gender, the genotypic frequencies were significantly associated with G460T polymorphism in men (p < 0.01) and in women (p < 0.05). Furthermore, no relationship was found between clinical characteristics and ADD1 G460T genotypes. CONCLUSIONS The present study shows that the a-adducin G460T polymorphism is associated with EH. Our results suggest that this variant can be considered a genetic risk factor for hypertension in the Tunisian population.

Little evidence suggests an impact of vitamin D on bladder cancer risk in Caucasians. This study aimed to investigate association of plasma 25-hydroxyvitamin D (25-OHD) with urothelial bladder cancer (UBC) risk in Tunisians. A case-control study included 250 patients with UBC and 250 healthy controls. Plasma 25-OHD was assessed by a competitive chemiluminescence immunoassay. Vitamin D deficiency and insufficiency were defined as 25-OHD

The aim of this study was to investigate the relationship between the adiponectin levels and various characteristics of the metabolic syndrome (MS) in a sample of the Tunisian population. Three hundred and fifty-four individuals were included in this study. Body mass index, blood pressure, HDL-cholesterol, triglycerides, glucose, insulin, and adiponectin concentrations were measured. Insulin resistance was assessed by homeostasis model assessment of insulin resistance (HOMA-IR). MS was identified with the NCEP-ATP III criteria. Subjects with MS showed significantly lower adiponectin levels compared to those without MS. For both genders, the prevalence and the number of MS components increased significantly as the adiponectin concentrations decreased. Subjects with the lowest adiponectin quartile had an increased risk of MS adjusted for age, gender, and HOMA-IR. Our findings suggest that hypoadiponectinemia is strongly associated with the risk of MS independent of insulin resistance.

article i nfo Background: Apolipoproteins AI-CIII-AIV play important roles in the metabolism of triglycerides and high- density lipoprotein cholesterol. However, whether genetic variations in the ApoAI-CIII-AIV gene cluster are associated with the risk of myocardial infarction (MI) remains uncertain. In the present study, we examined a possible association of the ApoCIII SacI polymorphism in the ApoAI-CIII-AIV gene cluster with lipid parameters and MI in a sample of the Tunisian population. Methods:A total of 326 Tunisian patients with MI and 361 controls were included in the study. Genotypes were determined by polymerase chain reaction — restriction fragment length polymorphism (PCR-RFLP) analysis. Results: A significant difference in genotype distribution and allele frequency was observed between patients and controls. At the multivariate analysis after adjustment for traditional vascular risk factors, the ApoCIII SacI polymorphism was significantly associated with MI, according to co-dominant and dominant models (co- dominant model odds ratio (OR): 1.53, 95% confidence interval (CI): 1.0-2.35, p=0.04; dominant model OR: 2.02, 95% CI: 1.11-3.67, p=0.02). The MI patient group showed a significant higher frequency of the S2 allele compared to the controls (10.2% vs. 6.5%; OR: 1.64, 95% CI: 1.10-2.47, p=0.01). There was no statistically significant association between ApoAI-CIII-AIV cluster gene polymorphism and lipid, lipoprotein, and apolipoprotein levels in both MI patients and controls. Conclusion: In the current study, a significant association between the ApoCIII SacI polymorphism (presence of S2 allele) and MI in the Tunisian population was found.

Objectives Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) mediates endothelium-dependent vasodilatation and antithrombotic action. Controversial results regarding the association of eNOS gene (NOS3) polymorphisms with hypertension have been reported. In the present study, we examined a possible association between the 27-base pair (bp) repeat polymorphism in intron 4 of the NOS3 gene and hypertension in a sample of the Tunisian population. Design and methods A total of 295 Tunisian patients with hypertension and 395 healthy controls were included in the study. The NOS3 gene intron 4a4b variable number of tandem repeats polymorphism was analyzed by PCR. Results A significant differences in genotype distribution and allele frequency was observed between patients and controls. Patients with hypertension had a frequency of 6.4% for the 4a4a genotype, 32.7% for the 4a4b genotype and 60.9% for the 4b4b genotype. The controls had a frequency of only 2.3% for the 4a4a genotype, 28.4% for the 4a4b genotype and 69.4% for the 4b4b genotype (χ2 = 11.81, p = 0.003). The hypertension patient group showed a significant higher frequency of the 4a allele compared to the controls (0.23 vs. 0.16; χ2 = 8.61, p = 0.003). The odds ratio of hypertension for 4a vs 4b allele frequencies was statistically significant 1.66 [1.09–2.53] at 95% CI, p = 0.01 in males, whereas it was non-significant in females (1.23 [0.84–1.81], p = 0.26). Conclusion The present study showed a significant and independent association between the NOS34a4b gene polymorphism (presence of 4a allele) and hypertension in the Tunisian population.

Objectives The aim of this study was to examine the association of the G-2548A polymorphism of the human leptin gene (LEP) with body mass index (BMI), plasma leptin, insulin, and lipid parameters in a sample of Tunisian population. Design and methods Two hundred and twenty nine obese patients (BMI ≥ 30 kg/m2) were screened and compared to 251 normal weight subjects (BMI

Background Monocyte chemoattractant protein-1 (MCP-1; gene name CCL2 ) has been suggested to play an important role in the initiation of atherosclerosis by recruiting monocytes to sites of injured endothelium. Recently, single nucleotide polymorphisms (SNPs) in the MCP-1 regulatory region have been identified. Controversial results regarding the association of the − 2518G/A polymorphism of the MCP-1 gene with coronary artery disease (CAD) have been reported. In the present study, we examined a possible association between the − 2518G/A polymorphism of the MCP-1 gene and myocardial infarction (MI) in a sample of the Tunisian population. Methods A total of 319 Tunisian patients with MI and 467 healthy controls were included in the study. The SNP of the MCP-1 gene was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results Patients with MI had significantly higher frequency of the AG + GG genotypes compared to controls [42.9% vs. 35.8%; OR (95%CI), 1.34 (1.00–1.79); p = 0.04]. The MI patient group showed a significant higher frequency of the G allele compared to the controls [0.242 vs. 0.195; OR (95%CI), 1.31(1.02–1.68), p = 0.03]. The association between the − 2518G/A polymorphism of the MCP-1 gene and MI was no longer significant after adjustment for other well-established risk factors. Conclusion The present study showed a significant but not independent association between the − 2518G/A polymorphism of the MCP-1 gene (presence of G allele) and MI in the Tunisian population.

To examine the association of a common -2548G/A (rs7799039) promoter variant of the human leptin gene (LEP) with obesity or body mass index (BMI) and its associated phenotypes such as blood pressure variability and the prevalence of hypertension in a sample of the Tunisian population.Two hundred and twenty-nine obese patients were screened and compared with 251 normal weight subjects. The -2548G/A LEP polymorphism was analysed by PCR-RFLP procedure.No significant association was found between the -2548G/A polymorphism and obesity or BMI. However, in obese patients subjects with AA genotype had significantly higher systolic (p = 0.003) and diastolic (p = 0.002) blood pressure compared with those with GA or GG genotypes. Stratified analysis by gender revealed that male patients but not female homozygous for -2548A allele exhibited significantly increased systolic (p = 0.01) and diastolic (p0.001) blood pressure than did carriers of -2548G allele. Multiple linear regression analysis revealed that AA genotype significantly affect systolic and diastolic blood pressure in obese men. Additionally, significant association between AA genotype and higher prevalence of hypertension was found in male patients (p = 0.03).The present study showed that the -2548G/A LEP polymorphism is associated with blood pressure in obese male patients.

Objective: Human paraoxonase 1 (PON1) is an HDL-associated enzyme with anti-oxidant/anti-inflammatory properties that has been suggested to play an important protective role against coronary artery disease (CAD). The PON1 promoter -108C/T polymorphism has been analyzed in numerous association studies as a genetic marker for CAD, however, with controversial results. The aim of this study was to evaluate the association of PON-1 promoter -108C/T polymorphism with the risk of myocardial infarction (MI) in the Tunisian male population.Methods: A total of 815 subjects were recruited, including 318 healthy controls and 497 MI patients. Genotypes were determined by PCR-RFLP method. Genotype/allele frequencies were compared in patients and controls using the chi-square test.Results: Genotype distributions and allele frequencies of PON-1 promoter -108C/T polymorphism were different among the control and MI groups. Patients with MI had significantly higher frequency of the TT genotype compared to controls [29.2% vs. 25.5%; OR (95% CI), 1.67 (1.52-2.49); p=0.010]. The MI patient group showed a significant higher frequency of the T allele compared to the controls [0.56 vs. 0.51; χConclusion: The present study showed a significant and independent association between the PON-1 promoter -108C/T polymorphism and MI in the Tunisian male population.

Background Coronary artery disease is influenced by both environmental and genetic factors. Current evidence shows that the CD40-CD40 ligand (CD40-CD40L) system plays a crucial role in the development, progression and outcome of acute coronary syndrome. A single nucleotide polymorphism (SNP) located at position –1 in the Kozak sequence of the CD40 gene (rs1883832; C>T) has been associated with the development of acute coronary syndrome. The purpose of the study was to explore the association between the C/T (–1) single nucleotide polymorphism in the CD40 gene and myocar-dial infarction (MI) in the Tunisian male population. Methods A total of 273 unrelated Tunisian patients with MI and 219 healthy controls were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Clinical parameters such as fasting serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, and plasma glucose were detected by autoanalyzer assay. Weight, height and blood pressure (BP) were measured and body mass index (BMI) was calculated. Results Patients with MI had significantly higher frequency of the TT genotypes compared to controls (12.5% vs. 5.9%; OR=1.43, 95% CI: 1.08 – 1. 89, p=0.011). The MI patient group showed a significant higher frequency of the T allele compared to the controls (0.33 vs. 0.26; OR=1.45, 95% CI: 1.09 – 1.94, p=0.008). The association between the C/T (–1) single nucleotide polymorphism in the CD40 gene and MI remained significant after adjustment for other well-established cardiovascular risk factors. Conclusion Our study suggests that C/T (–1) single nucleotide polymorphism in the CD40 gene might contribute to the susceptibility to MI in the Tunisian male population. Further replication with larger numbers, and populations of different ethnicities, are needed to confirm our finding.

BackgroundCoronary artery disease (CAD), the leading cause of death worldwide, is a multifactorial disease arising from the complex interplay of genetic and environmental factors. Paraoxonase 1 (PON1) polymorphisms have been implicated as risk factors for CAD, but the results of genetic association studies on the related phenotype of CAD are inconclusive. The aim of the present study was to investigate the association between the PON1 promoter –108 C>T (rs705381) and the coding region Gln192Arg (Q192R, rs662) and Leu55Met (L55M, rs854560) variants with myocardial infarction (MI) in a sample of the Tunisian population.MethodsA total of 382 unrelated MI patients and 380 healthy controls were enrolled in this study. Genotyping was performed by the polymerase chain reaction and restriction fragment length polymorphism method (PCRRFLP). The frequencies of the alleles and genotypes between MI patients and controls were compared by the chi-square test.ResultsGenotype distribution and allele frequencies of L55M were similar among the control and MI groups. The PON1-Q192R and –108 C>T genotypes exhibited significant differences in allele and genotype frequencies among the MI and control groups. At PON1-192 locus, there were significant differences between patients and controls (pT polymorphism was found to be a risk marker for MI (OR=1.29, CI: 1.05 – 1.58; p=0.011).ConclusionsThe present study showed a significant and independent association between the PON1 Q192R and – 108 C>T polymorphisms and MI in the Tunisian male population.

The prothrombin is the precursor of the serine protease thrombin, a key enzyme in homeostasis. Prothrombin G20210A polymorphism (rs1799963) was described as a moderate risk factor for venous thrombosis because this mutation is associated with prothrombin elevated levels which may lead to an imbalance between the procoagulant, anticoagulant, and fibrinolytic system. 20210A carriers have an increased risk of thrombosis. In this study, we proposed to determine the prevalence of 20210A prothrombin variant among Tunisian population, and to evaluate the potential relevance of this variant with myocardial infarction. This study included 1290 unrelated Tunisians (1007 male and 283 female) divided in two groups: Four hundred and eighty-seven MI patients (mean age: 52.64 ± 8.98 years) and 803 apparently healthy controls (mean age: 51 ± 8.99). The prothrombin G20210A polymorphism was carried out by polymerase chain reaction/restriction fragment length polymorphism (PCR–RFLP) analysis. The distribution of genotypes was in accordance with Hardy–Weinberg equilibrium (p > 0.05). A significant difference in genotype distribution and allele frequency was observed between patients and controls. Male patients with MI had a frequency of 97 % for GG genotype and 3 % for GA+AA genotypes. The control group had a frequency of 99 % for the GG genotype and 1 % for the GA+AA genotypes which is significantly lower than the frequency found in patients (p = 0.01). The same genotype frequencies were found in women (p = 0.032). The MI patient group showed a significantly higher frequency of 20210A allele compared to controls 0.02 versus 0.01 [OR = 3.60 (95 % CI = 1.29–10.53), p = 0.005] in men and 0.015 versus 0.068 [OR = 4.68 (95 % CI = 1.60–14.26), p = 0.001] in women. Our work showed a significant but not independent association between the G20210A polymorphism of the prothrombin gene and MI in the Tunisian population.

The aim of the study was to test whether the VDR FokI polymorphism is associated with the risk of urothelial bladder cancer (UBC) in Tunisians. The study included 200 unrelated patients with UBC and 200 healthy controls. Genotyping of the VDR FokI polymorphism was determined by PCR-RFLP method. Plasma 25-hydroxyvitamin D concentrations were measured by immunoassay. Binary logistic regression model was applied to test how the association of VDR FokI polymorphism is independent of potential confounding factors. Genotype distribution (FF, 45 vs. 55 %; Ff, 52.1 vs. 47.9 %, and ff, 12 vs. 5.5 %, respectively) and allele frequencies (F, 66.5 vs. 74.8 % and f, 33.5 vs. 25.2 %, respectively) were significantly different between UBC patients and controls. The "ff" genotype [OR (95 % CI), 2.66 (1.24-5.73); p = 0.012] and "f" allele [1.49 (1.09-2.02); p = 0.010] were associated with increased risk of UBC. The association remained significant in multivariate analysis. Stratified analyses showed that VDR FokI polymorphism is only associated with UBC risk in ever-smokers, subjects exposed to chemical carcinogens and those with plasma 25-hydroxyvitamin D over 12 μg/L. The "f" allele of VDR FokI polymorphism is associated with a higher risk of UBC in Tunisians, especially in smokers as well as subjects with occupational exposition and subjects without vitamin D deficiency. These results should be replicated in other ethnic groups and the influence of other genetic factors and environments on this association should be investigated.

We determined the frequencies of apolipoprotein E (apo E) gene alleles and examined the association between apo E polymorphism and lipid parameters in a sample of the Tunisian population.Apo E polymorphism was investigated using PCR, and plasma lipid parameters were measured in 122 men and 111 women aged 35 to 87 years.The allele frequencies were epsilon2: 7.3%, epsilon3: 84.6%, and epsilon4: 8.1%. Apo E polymorphism was associated with significant differences (P0.001) in total cholesterol, apo B and LDL cholesterol in both men and women. epsilon2 carriers had the lowest mean total cholesterol, apo B and LDL-C concentrations, and subjects with the epsilon4 allele had the highest levels. Triglycerides levels increased with the epsilon4 allele, but this did not reach statistical significance. These results remained unchanged after adjustment for age, body mass index, sex, hypertension, diabetes and smoking. However, in obese subjects (BMI30 kg/m2), TG concentrations were significantly lower in individuals homozygous for the epsilon3 allele compared to those with the alleles epsilon2 or epsilon4.In this sample of the Tunisian population, the distribution of apo E gene alleles is similar to that observed in Southern European populations with low prevalence of the epsilon4 allele. Variations in the apo E gene play a role in determining plasma lipid levels. These data also suggest that effects of apo E alleles on lipids levels are partly dependent on environmental variables such as BMI. These findings highlight the importance of the gene/environment interaction on the deleterious effect of obesity on cardiovascular risk factors.

Background ABCB1, also known as P-glycoprotein (P-gp), is the most well studied member of the ATP-binding cassette (ABC) family of transporters. ABCB1 is embedded in the lumen-facing epithelial cell membranes of many biological barriers of organisms and is an efficient ATP-dependent efflux pump that is mainly responsible for the removal of numerous xenobiotics. However, ABCB1 may play a role in additional, more intrinsic functions. A number of researches have evaluated the association between the ABCB1 polymorphism and the lipid-lowering response of statins, but the results have been inconclusive. The aim of the present study was to investigate possible association between the ABCB1 G2677 W polymorphism and changes in lipids in patients following atorvastatin treatment. Methods A total of 122 unrelated coronary patients (54.06 ± 8.74 years old) were enrolled in this study and given 40 mg of atorvastatin daily for 8 weeks. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) serum levels were measured at baseline and after 8 weeks of treatment. ABCB1 G2677 W polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results The 8-week treatment with atorvastatin significantly reduced TC (1.37 ± 0.27 g/L vs. 1.87 ± 0.47 g/L; P = 0.03), TG (1.50 ± 0.30 g/L vs. 1.99 ± 0.70 g/L, P = 0.002), and LDL (0.77 ± 0.27 g/L vs. 1.15 ± 0.36 g/L, P = 0.001) levels, but there was no statistical difference among patients with wild type ABCB1 G2677 W in the lipid-lowering efficacy of atorvastatin. Conclusion The present study found that the ABCB1 G2677 W polymorphism does not affect the lipid-lowering efficacy of atorvastatin.

IntroductionParaoxonase 2 (PON2) has antioxidant properties similar to paraoxonase-1 and paraoxonase-3. However, in contrast to paraoxonase-1 and paraoxonase-3, paraoxonase-2 is not associated with high-density lipoproteins and may only exert its antioxidant function at the cellular level. PON2 may also play a role in the pathogenesis of arterial thrombosis and atherosclerosis. The purpose of the present study was to investigate the possible association between the Cys311Ser polymorphism of PON2 gene and myocardial infarction (MI) in the Tunisian male populationMaterials and methodsA total of 700 unrelated Tunisian subjects including 321 patients with MI and 379 healthy controls were included in this study. Genomic DNA was extracted from peripheral blood leukocytes according to standard methods. PON2 genotypes were determined by PCRRFLP method.ResultsA significant difference in genotype distribution and allele frequencies was observed between MI patients and controls. Patients with MI had a frequency of 17.1% for CC genotype, 45.8% for the CS genotype and 37.1% for the SS genotype. The controls had a frequency of 26.1% for the CC genotype, 45.6% for the CS genotype and 28.2% for the SS genotype (χ2=10.58; p=0.005). The MI patient group showed a significantly higher frequency of the S allele compared to the controls (0.60 vs 0.51; χ2 =11.16; p

Introduction Le syndrome de Sjorgen primitif (SSP) est considere comme l’une des connectivites les plus frequentes avec une prevalence allant de 0,6 a 1,7 %. Le SSP est caracterise par une atteinte glandulaire exocrine responsable d’un syndrome sec. L’interleukine-10 est une cytokine pleiotrope incriminee dans la physiopathologie du SPP. Le but de notre etude etait de comparer le taux moyen d’interleukine-10 chez des patients atteints d’un SSP et des temoins sains dans une population tunisienne, de determiner les frequences genotypiques de trois polymorphismes : −1082 (G/A) ; −819 (C/T) ; et −592 (C/A) et d’etudier les associations entre les haplotypes et la maladie. Materiels et methodes Ont ete inclus 242 sujets repartis en 84 malades atteints de SSP (repondant aux criteres de l’AECG et/ou de l’ACR 2012) vus dans un service de medecine interne et 158 sujets temoins. Le dosage de l’interleukine-10 etait realise selon la methode ELISA. Les polymorphismes du gene de l’interleukine-10 ont ete etudies selon la technique PCR-RFLP. Resultats Le taux moyen d’interleukine-10 etait significativement plus bas chez les malades atteints de SSP (23,71 pg/mL, n = 73) compare aux sujets temoins (42,27 pg/mL, n = 60) avec un p = 0,01. La frequence genotypique de notre population respectait l’equilibre de Hardy–Weinberg chez les sujets malades et chez les temoins. Chez les malades atteints de SSP la frequence genotypique pour le polymorphisme −592 C/A etait de 53 % pour le genotype CC 41 % pour le genotype CA et 6 % pour le genotype AA. Pour les sujets temoins, ces frequences etaient respectivement de 60,3 %, 32,9 % et 6,8 %. La frequence genotypique du polymorphisme −1082 G/A des sujets malades etaient de 29,6 % pour le genotype AA, 63 % pour le genotype AG et 7,4 % pour le genotype GG. Chez les sujets temoins, ces frequences etaient respectivement de 41,5 %, 52,1 % et 6,3 %. La frequence genotypique du polymorphisme −819 C/T des sujets malades etaient de 47,6 % pour le genotype CC, 43,9 % pour le genotype CT et 8,5 % pour le genotype TT. Chez les sujets temoins, ces frequences etaient respectivement de 43,2 %, 49,2 % et 7,6 %. Aucune difference significative n’a ete observee entre les sujets malades et temoins dans les trois polymorphismes. L’analyse statistique realisee a montre qu’il n’existait ni d’haplotype protecteur ni aggravant. Cependant, l’haplotype ATC semble avoir un effet protecteur chez les sujets temoins ( p = 0,06, OR = 0,20). Conclusion Il a ete demontre dans de precedentes etudes que le taux moyen d’interleukine-10 etait significativement plus eleve chez les sujets malades que chez les temoins. Dans notre etude, l’interleukine-10 etait a un taux moyen statistiquement plus bas chez les malades. Les trois polymorphismes du gene de l’interleukine-10 ne sont pas associes au SSP chez la population tunisienne. Cette difference pourrait etre expliquee par les variations alleliques ou par les differences ethniques.

Background and aims Peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) is a transcriptional co-activator involved in adaptive thermogenesis, skeletal muscle metabolism, fatty acid oxidation, and gluconeogenesis. Several studies have suggested that the common PGC-1α polymorphism Gly482Ser (rs8192678) may be associated with risk of type 2 diabetes (T2D), with conflicting results. The aim of this study was to analyze whether the Gly482Ser variant is a risk factor for development of T2D in Tunisian population. Methods In a case–control study 487 unrelated patients with type 2 diabetes and 402 apparently healthy controls were recruited from January 2008 to August 2010. The Gly482Ser polymorphism was determined by PCR-RFLP analysis. Results A significant difference in genotypes distribution was observed between patients (Gly/Gly: 34.1%; Gly/Ser: 47.1%; Ser/Ser: 18.5%) and controls (Gly/Gly: 43.8%; Gly/Ser: 42.3%; Ser/Ser: 13.9%) ( χ 2 = 9.44, p = 0.009). The T2D patient group showed a significant higher frequency of the Ser allele compared to the controls (43% vs. 34%; OR: 1.35, 95% [CI]: 1.11–1.65, p = 0.002). The association between the Gly482Ser polymorphism and T2D remained significant after adjustment for other well-established cardiovascular risk factors. Conclusions In the current study, a significant and independent association between the Gly482Ser polymorphism (rs8192678) of the PGC-1α gene and T2D in the Tunisian population was found.

Behcet's disease (BD) is a multisystem inflammatory disease characterized by recurrent orogenital ulceration, ocular inflammation and skin lesions. Reduced plasma nitric oxide (NO) levels in patients with BD have been implicated in the development of the endothelial abnormalities and thrombotic complications occurring in these patients. Polymorphisms in the endothelial nitric oxide synthase gene (NOS3) have been inconsistently associated with BD. This inconsistency may derive from population stratification secondary to ethnic diversity, and consideration limited to only one rather than combinations of polymorphisms. We studied three genetic variations in the NOS3 gene: a single nucleotide polymorphism in the promoter region -786T>C, in exon 7 (Glu298Asp), and a variable number of tandem repeats in intron 4 (4a4b) of the NOS3 gene in 100 unrelated Tunisian patients with BD and 148 healthy controls. In addition, we also examined the association of NOS3 gene haplotypes with BD. Analyses of the Glu298Asp, -786T>C and 4a4b polymorphisms were made by the polymerase chain reaction (PCR) restriction fragment length polymorphism technique and PCR genotyping, respectively. The distribution of the Glu298Asp genotype differed significantly between patients with BD and controls (P = 0.01). Allele Asp298 was significantly more frequent in patients with BD than in controls (P = 0.005, OR = 1.70, 95% CI 1.14-2.54). In contrast, distribution of alleles and genotypes of -786T>C and 4a4b polymorphisms was not different between the control and BD group. However, the frequency of Asp-T-4b haplotype was significantly higher in patients with BD than in healthy controls. By gender, the signification remained only for heterozygous men (P = 0.03) and homozygous women (P = 0.02). These results suggest that Glu298Asp polymorphism of the NOS3 gene is associated with BD susceptibility in Tunisian patients.

Purpose Development of a validated risk prediction model for cardiovascular death in coronary patients is a high priority for strategies of therapy. We sought to validate and recalibrate of the SCORE (Systematic coronary risk evaluation) risk chart based on Tunisian national mortality data and average major cardiovascular risk factor levels. Methods Baseline data were collected between 1997 and 2004 in 146 male patients aged 52.4 ± 9 years hospitalized with STEMI treated with fibrinolysis in 68 % of patients and not revascularized early in 32% of patients. Vital status was checked and causes of death were obtained in 2011 after a mean follow up of 9.6 years. The expected cardiovascular mortality was calculated by applying the SCORE equation for high risk populations on the basis of the level of risk factors in the total population, in the diabetic and non-diabetic population and was compared with the observed mortality in each group. Correction factor was calculated for each group. Univariate analysis was used for statistical analysis. The optimum threshold of SCORE , allowing for an optimal sensitivity and specificity, was determined by the ROC curve (receiver operating characteristic). For risk thresholds 5% and that determined from the ROC curve of the European SCORE sensitivity, specificity values were calculated. Results The total number of cardiovascular death at 10 years is 18 with a mortality of 12.3%. The average of SCORE in our population was 8.73+/-5.12% with extremes ranging from 1 to 32%. The European SCORE was strongly correlated in our cohort to the occurrence of cardiovascular death at 10 years (p SCORE is calculated to 2.7 in diabetic group, 1 in non-diabetic group and 1.4 for the total population. The ROC curve has a c index ( AUC ) = 0.73 corresponding to the risk threshold of 9.12%. The relative risk of cardiovascular death at 10 years of SCORE for the 9.12% threshold is calculated at 3.6. For the risk threshold for 9.12%, sensitivity was calculated at 66.7% and specificity at 68.8%. For the risk threshold for 5%, sensitivity was calculated at 94.9% and specificity at 17.96%. Conclusion SCORE is validated in coronary male Tunisian patients with and recalibrated using correction factors. Validation on a larger population and multi-ethnic remains our future desire.

article i nfo Article history: Objectives: In the present study, we examined a possible association between the PON1 Q192R and L55M polymorphisms and myocardial infarction (MI) in a sample of the Tunisian population. Design and methods: Three hundred and ten patients with MI and 375 controls were recruited. Paraoxonase gene polymorphisms at codon 192 and 55 were analyzed by PCR-RFLP. Results: Genotype distributions and allele frequencies of L55M were similar among the control and MI groups. For the Q192R polymorphism patients with MI had significantly higher frequency of the RR genotype compared to controls (17.1% vs. 10.9%; OR (95% CI), 1.93 (1.24-3.02); p=0.004). The MI patient group showed a significantly higher frequency of the R allele compared to the controls (38% vs. 30%; χ 2 =10.74, p=0.001). The association between the PON1 Q192R polymorphism and MI remained significant after adjustment for other well-established cardiovascular risk factors. Conclusions: The present study showed a significant and independent association between the PON1 Q192R polymorphism (presence of R allele) and MI in the Tunisian population.

Chemokines and their receptors are known to mediate inflammation and tissue damage in autoimmune disorders such as multiple sclerosis (MS). Multiple sclerosis is an inflammatory disease of the central nervous system, characterized by myelin damage and neurological complications. Monocyte chemoattractant protein-1 (MCP-1) interacts with the C–C chemokine receptor 2 (CCR2) and plays a role in the migration of leukocytes into the central nervous system, thus contributing to the T cell-mediated pathogenesis of MS. Genomic DNA obtained from 58 MS patients and 72 healthy controls was tested for the MCP-1 –2518 A > G and CCR2 Val64Ile polymorphisms using polymerase chain reaction–restriction fragment length polymorphism analysis. Neither the MCP-1 –2518G (p = 0.43) nor the CCR2 64Ile (p = 0.52) variant contributed to the risk of MS in Tunisians.

BACKGROUND Elevated total plasma homocysteine (tHcy) is an established risk factor for occlusive vascular disease and is thought to increase the risk of pregnancy loss, birth defects, and cognitive impairment in the elderly. OBJECTIVES To determine tHcy standard values and the prevalence of hyperhomocysteinemia (HHC) and to examine their association with demographic and life style factors in the Greater Tunis population. METHODS This cross-sectional study included 2712 subjects (1228 males and 1484 females) aged 35 - 70 years, living in the Greater Tunis region. tHcy was analyzed by a fluorescent polarizing immunoassay method. HHC was considered as tHcy > or = 15 micromol/L. RESULTS HHC was observed in 23.7% of subjects. Plasma tHcy was higher in males than females (median (5th - 95th percentile): 13.5 [8.75 - 26.3] micromol/L vs. 10.7 [6.94 - 19.6] micromol/L). The tHcy concentration was significantly increased in smokers, alcoholics, in subjects with vitamin B12 and folate deficiencies, and hyperuricemia. In multivariate analysis, HHC was associated with male gender, vitamin B12 deficiency, clearance of creatinine, alcohol consumption, and hyperuricemia. CONCLUSIONS HHC is common in Tunisian adults. Male gender, advanced age, renal insufficiency, low vitamin B12 status, hyperuricemia, and alcohol consumption are the main determinants of HHC in this population.

Aims Tumor necrosis factor α (TNFα) plays a key role in orchestrating the complex events involved in inflammation and immunity. Accordingly, TNF α has been implicated in a wide range of autoimmune and infectious diseases, but also in conditions such as obesity and insulin resistance. The aim of the present study was to investigate the association between the −863C/A polymorphism in the promoter of the TNFα gene and type 2 diabetes in the Tunisian population. Methods The polymorphism −863C/A in the TNFα gene was determined in 211 type 2 diabetes patients and 345 healthy controls using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analysis. Results A significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with type 2 diabetes had significantly higher frequency of the CA + AA genotypes compared to controls [35.5% vs. 22.3%; OR (95%CI), 1.91 (1.31–2.8); p = 0.001]. The type 2 diabetes patient group showed a significant higher frequency of the A allele compared to the controls (0.19 vs. 0.11; p = 0.001). After adjustment by a stepwise logistic regression method, hypertension, dyslipidemia, and CA + AA genotype were found to be significantly associated with T2D. Conclusion The present study showed a significant and independent association between the −863C/A polymorphism of the TNFα gene and type 2 diabetes in the Tunisian population.

Controversial results regarding the association of eNOS gene (NOS3) polymorphisms with myocardial infarction (MI) have been reported. This study investigated the relationship of the -786TC (rs2070744), 894GT (rs1799983) and 4a4b polymorphisms of the NOS3 gene with the presence of MI in the Tunisian population. In addition, we also examined the association of NOS3 gene haplotypes with MI in Tunisian subjects. A total of 303 patients with MI and 225 controls were included in the study. The 894GT and -786TC single nucleotide polymorphisms were analyzed by PCR-RFLP, and 4a4b polymorphism just for PCR. There was significant linkage disequilibrium between the three NOS3 polymorphisms (p0.0001). The genotype distribution and allele frequency of NOS3 4a4b, but not -786TC and 894GT, polymorphism was significantly different between MI patients and controls. The univariate logistic regression analysis showed a significant association of the 4a4b polymorphism and MI according to co-dominant, dominant and recessive models (co-dominant model OR: 4.38, 95%CI: 1.24-15.41; p=0.021, dominant model OR: 1.66, 95%CI: 1.14-2.42); p=0.007, and recessive model OR: 3.85, 95%CI: 1.10-13.47; p=0.035). The multivariate analysis, adjusted for traditional cardiovascular risk factors, revealed that the NOS3 4a4a genotype was an independent predisposing factor to MI, according to the models considered. In addition, a haplotype 7 (C-T-4a), (OR=12.05, p=0.010) was a risk factor of MI after controlling for classical risk factors. These finding suggest that the 4a4b polymorphism of the NOS3 gene was associated with MI in Tunisian patients.

Introduction The prothrombin is the precursor of the serine protease thrombin, a key enzyme in hemostasis and thrombosis. Prothrombin 20210GA polymorphism was described as a moderate risk factor for venous thrombosis because this mutation is associated with prothrombin elevated levels which may lead to an imbalance between the procoagulant, anticoagulant and fibrinolytic system. 20210GA curriers have an increased risk of thrombosis. In this study, we propsed to determine the prevalence of 20210GA prothrombin variant among Tunisian population, and to evaluate the potential relevance of this variant with myocardial infarction (MI). Methods This study included 1007 unrelated male Tunisians divided into 399 MI patients and 608 healthy controls. Both groups were aged between 35-70 years. The prothrombin 20210GA polymorphism was carried out by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) analysis. Results The distribution of genotypes was in accordance with Hardy-Weinberg equilibrium (P >0.05). A significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with MI had a frequency of 97% for GG genotype and 3% for GA + AA genotype. The control group had a frequency of 99% for the GG genotype and 1% for the GA + AA genotype (χ2=6.95, p=0.031). The MI patient group showed a significant higher frequency of the 20210A allele compared to the controls 0.02 vs. 0.01 [OR=3.60 (95% CI=1.29-10.53), p =0.005]. Conclusion Our work showed a significant association between the 20210GA polymorphism of the prothrombin gene and MI in the Tunisian population.

Introduction Coronary artery disease (CAD) is a multifactorial disease, its expression probably being influenced by the interaction of genetic and environmental risk factors. Genetic variation in the estrogen receptor-alpha gene (ERS1) has been associated with CAD in several populations worldwide, but results are still controversial. In the present study, we examined the association between the c.454-397T>C: PvuII restriction site (rs2234693) and c.454-351A>G: XbaI restriction site (rs9340799) polymorphisms (SNPs) and myocardial infarction (MI) in a sample of the Tunisian population. Material and methods The case group included 294 patients with MI, and the control group comprised 275 individuals with angiographically normal coronary arteries and without signs or symptoms of MI. ESR1 PvuII and XbaI polymorphism was determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. Results Genotype distributions of the SNPs in the control and patient groups were consistent with those expected for samples in Hardy-Weinberg equilibrium (p> 0.05). The Genotype distribution and the relative allelic frequencies of the -397T>C and - 351A>G polymorphisms were not significantly different between the control and patient groups (p=NS). Moreover, the odds ratio for MI associated with the c.454-397C (OR=1.02, 95% CI 0.81-1.30), and c.454-351G (OR=1.24, 95% CI 0.98-1.58) variants failed to reach statistical significance. Conclusion In the current study, we were unable to demonstrate a significant association of the ESR1 c.454-397T>C and c.454-351A>G polymorphisms with MI. These results do not support the extent of risk associated with developing MI previously reported for the ESR1 c.454-397T>C and c.454-351A>G polymorphisms.

SUMMARY Background: We investigated the interaction between the G protein β3 subunit (GNB3) C825T variant and angiotensin converting enzyme (ACE) Insertion/Deletion (I/D) polymorphism in hypertensive Tunisian population. Methods: Analyses of ACE and GNB3 genotypes were performed in 388 hypertensive patients and 425 healthy controls by polymerase chain reaction-restriction fragment length polymorphism. The plasma ACE activity was determined by a spectrophotometric method. Results: The ACE genotype distribution and allele frequencies were not significantly different between the hypertensive and normotensive subjects (p > 0.05). This polymorphism was not associated with hypertension (HTA) (OR = 0.93, 95% CI = 0.75 - 1.15; p = 0.50). In cases, subjects carrying the DD genotype exhibited higher plasma ACE activity than those with ID and II genotypes (p = 0.001). In this group, a linear regression analysis revealed that the ACE I/D polymorphism is independently associated with plasma ACE activity (p = 0.017). The genotypic distribution and allelic frequencies of the GNB3 C825T polymorphism were not significantly different between the two groups. This polymorphism was found to have no effect on the risk of HTA (OR = 1.14, 95% CI = 0.93 - 1.39; p = 0.21). We did not observe a significant interaction between the GNB3 gene and the ACE gene with HTA. Conclusions: In this study, the I/D polymorphism is a significant independent predictor for variability of plasma ACE activity but the ACE I/D and GNB3 C825T polymorphisms are not significant factors for HTA in the Tunisian population. Moreover, we found no interaction between ACE D allele and GNB3 825T allele solely or combined with respect to HTA in the Tunisian population. (Clin. Lab. 2013;59:85-92. DOI: 10.7754/Clin.Lab.2013.111105)

Background Beyond its critical function in calcium homeostasis, vitamin D has recently been found to play an important role in the modulation of the immune/inflammation system. Increasing numbers of study have established that vitamin D insufficiency contributes to a number of diseases, suggesting a range of physiological functions of vitamin D. Recent findings seem to show that low vitamin D levels in patients with Sjogren Syndrom could be associated with severe complications such as peripheral neuropathy. Objectives The purpose of this study was to evaluate plasma vitamin D level in Primary Sjogren9s Syndrome (PSS) and comparing it with healthy controls. Methods North Africans patients (Tunisian patients) with PSS were diagnosed in an internal medicine department. All patients with PSS meet the revised AECG criteria 2002 and/or ACR proposed criteria 2012. We proceed in this prospective study with a comparison of plasma vitamin D between two groups, with a matched age and sex, one of patients with a Primary Sjogren9s Syndrome (PSS) and a second of healthy control subjects. Sixty six patients with PSS were enrolled. Sex ratio was 0.11 (59 female (89.4%) and 7 male (10.6%)).Mean age at diagnosis was 49.07 years ±12.56 (range 26 -73years). Forty eight healthy controls were included. Sex ratio was 0, 14 (42 females (87.5%) and 6 males (12.5%). Registration and statistical analysis of data were done with SPSS. Plasma 25-hydroxyvitamin D (25-OHD) concentrations were measured by a competitive chemiluminescence immunoassay using the Liaison Analyzer (DiaSorin Inc., Stillwater, MN). The inter-assay CV was below 10%. Vitamin D deficiency was defined according to the most recent cut-points defined by The Institute of Medicine as 25-OHD concentrations Results Plasma vitamin D level of PSS patients was insufficient in 42.2% of cases (plasma vitamin D level Conclusions The incidence of vitamin D deficiency seems more important for PSS patients than healthy controls. It might be interesting to study these patients to examine the outcome of the disease and its severity after a vitamin D supplementation therapy. Disclosure of Interest None declared

Background After myocardial infarction, patients have a very heterogeneous risk of cardiovascular death and/or reinfarction. Furthermore, no genetic approach score, as part of secondary prevention, was found in the literature. Aim This is a prospective longitudinal study (mean follow up of 9.6 years) including 146 patients, hospitalized between August 1997 and August 2004 for a myocardial infarction (MI) who survived the 30 first day after the MI. Depending on the composite event cardiovascular death and/or myocardial infarction, the genetic score was derived from 43 single nucleotide polymorphisms (SNP) belonging to 26 different genes. In the same study 3 clinical and biological scores were calculated (European SCORE, Hard coronary heart disease and coronary heart death score of Framingham scores). A multivariate analysis using logistic regression was used. Results Mortality at 10 years was 12.3% with a median time of 5.2± 4.8 years. The incidence of the composite event cardiovascular death and/or myocardial infarction was 23.4% with a mean of 8.4±4.1 years.The genetic score predicting the composite event cardiovascular death and/or myocardial infarction is an equation that included age (OR=1.04, 95% CI: 0.98, 1.1) and the following polymorphisms eNOS894 (OR=1.87, 95%: 0.64, 5.43); rs2781665AT arginase (OR = 1.63, 95% CI: 0.69, 3.85); 45TG adiponectin (OR=1.62, 95% CI: 0.65,4.02); eNOS4a4b (OR=1.29, 95% CI: 0.53, 3.14) and MTP (OR=0.78, 95% CI: 0.35,1.74). The clinical and biological scores were all correlated with the long-term corrsponding predicted. Correction factors were calculated for each score. The genetic score had the best reliability with a Sensitivity = 73.3%, a Specificity = 61.3%, a predictive positive value =31.11%, a predictive negative value = 90.74%. Conclusion It seems that using a genetic score provides a good prediction of event cardiovascular death and/or myocardial infarction at long term. A validation of our genetic score and a combined clinical-genetic approach to a large population remains our future hope (table next page). Abstract 0025 – Table: Genetic factor tested in univariate analysis Genetic factors Cardiovascular death P non fatal MI Composite event Âge a l’inclusion 0,002 0,19 0,012 MTP 0,23 0,09 0,053 XbaI 0,83 0,03 0,1 MspI 0,54 0,25 0,54 PPAR 0,85 1 0,74 Prostacycline synthase 0,43 0,44 0,19 Insertion / delection(ApoB) 0,5 0,75 0,98 Apo CIII 0,05 0,17 0,2 Apo AI 0,77 0,79 0,69 EcoRI 0,27 0,5 0,79 Apo E 0,83 0,17 0,32 LFABP 0,46 0,3 0,85 eCNOS786 0,81 0,63 0,81 eNOS894 0,76 0,3 0,22 eNOS4a4b 0,43 0,05 0,44 MS 0,64 0,64 0,48 CYP1A1 0,88 0,47 0,93 MCP1 0,44 0,48 0,36 leptine 223A/G 0,84 0,085 0,29 leptine 2548G/A 0,43 0,62 0,81 Enzyme de conversion 0,001 0,76 0,38 Bradykinine 0,3 0,24 0,21 CD14 0,64 0,34 0,3 Andino45TG 1 0,03 0,02 rs2781666GT 0,005 0,22 0,39 Apo A51131CT 0,89 0,36 0,72 PON1Q192R 0,16 0,31 0,25 ApoA 51131CT 0,89 0,36 0,72 CBS ins/del 0,68 0,68 0,75 rs2781665AT 0,04 0,77 0,19 CCR2 0,92 0,65 0,81 CBS1080 0,98 0,55 0,57 rs17599586CT 0,63 0,95 0,89 PON2 0,82 0,52 0,43 res420 0,56 0,58 0,7 PPARC161T 0,001 0,4 0,002 rs2781668 0,74 0,76 0,65 TNF863CA 0,81 0,02 0,09 TNF1031TC 0,94 0,71 0,65 PON1L55M 0,6 0,69 0,58 Adiponectine4522CT 0,22 0,32 0,48 TNF308 0,52 0,74 0,56 MTHFRC337 0,38 0,45 0,93 MTHFR1298 0,12 0,12 0,12 MI : Myocardial infarction. Full-size table Table options View in workspace Download as CSV

Objectives The aim of the present study was to investigate the association between CCR2-Val64Ile and CCR5-Δ32 variants and the estimation of haplotypes with MI in a sample of the Tunisian population. Design and methods A total of 290 unrelated MI patients and 282 healthy controls were studied. The CCR2-Val64Ile and CCR5-Δ32 variants were analyzed by PCR-RFLP. Results Subjects carrying at least one copy of the CCR5-deletion allele were significantly more common in the control group, suggesting an atheroprotective effect (adjusted OR = 0.44, 95% CI = 0.28–0.72, p = 0.001). Haplotype analysis showed that MI patients had significantly less 64Val-Del haplotype (9.9% vs. 21.3%, OR = 0.30, 95% CI = 0.21–0.43, p Conclusion A protective effect of the CCR5-Δ32 polymorphism against MI in the Tunisian population was found.

Many studies have shown that hyperhomocysteinemia may be an independent risk factor for coronary artery disease. However, not all prospective studies support an association between elevated plasma homocysteine levels and coronary artery disease. Nitric oxide (NO) plays a relevant role in various events during atherogenesis, and in vitro data suggest that NO may modulate total homocysteine (tHcy) concentrations, whereas polymorphisms of the endothelial nitric oxide (NOS3) gene have been reported to be related to an increased risk of myocardial infarction (MI) and hyperhomocysteinemia, but the results have been controversial. We hypothesized that the NOS3 synthase 4a4b VNTR polymorphism is a determinant of tHcy concentrations and tested this in 310 patients with MI and 250 controls. The NOS3 gene intron 4a4b VNTR polymorphism was analyzed by polymerase chain reaction analysis. There was no significant difference in the homocysteine levels between patients with MI and controls. The frequencies of the NOS34b4b, 4b4a, and 4a4a genotypes in the MI group were significantly different from those in the control group. In patients with MI, plasma tHcy concentrations were significantly different among the NOS3 genotypes (13.5±4.5, 18.5±3.9, and 20.4±2.1 μmol/L for 4b4b, 4a4b, and 4a4a genotypes, respectively; P