INTRODUCTION:Systemic sclerosis is a rare autoimmune disease characterized by microcirculation abnormalities and fibrosis of the skin and/or internal organs. Both genetic and environmental factors are recognized contributors to AID development. Vitamin D, through its receptor, plays a role in immune regulation, and the VDR gene has been identified as a candidate for AID susceptibility. However, studies examining the relationship between VDR polymorphisms and AIDs have yielded conflicting results, often varying by ethnic background. OBJECTIF:The purpose of this study was to investigate the association of FokI and BsmI polymorphisms of the VDR gene with systemic sclerosis in a Tunisian population. METHODS:A case-control study was conducted, involving 68 SSc patients and 190 healthy controls. Genotyping of the two polymorphisms was performed using restriction fragment length polymorphism polymerase chain reaction, and data analysis was conducted via SPSS for Windows (version 28.0). RESULTS:Results showed significant differences between SSc patients and controls for both polymorphisms. The BsmI bb genotype (0.28 vs. 0.12; p=0.004) and b allele (0.49 vs. 0.36; p=0.014) were more frequent in SSc patients. Conversely, the FokI Ff (0.54 vs. 0.41; p=0.007) and ff (0.15 vs. 0.06; p=0.008) genotypes, along with the f allele (0.42 vs. 0.26; p<0.001), were more common in the control group. CONCLUSION:The BsmI polymorphism was associated with increased genetic predisposition to SSc, whereas the FokI polymorphism appeared to confer protection in the studied population.

Sjögren’s syndrome is a chronic autoimmune disorder characterized by dysfunction of exocrine glands, primarily manifesting as xerostomia and keratoconjunctivitis sicca. Although its pathogenesis remains incompletely elucidated, microRNAs (miRNAs) have been increasingly recognized as potential regulators of immune homeostasis. These small non-coding RNAs exert epigenetic control by modulating gene expression post-transcriptionally, primarily through mRNA degradation or translational repression, thereby influencing key inflammatory and immunological pathways. In this case-control study, we investigated the association of three miRNA gene polymorphisms (rs2910164 in miR-146a, rs11614913 in miR-196a2, and rs3746444 in miR-499) with susceptibility to Sjögren’s syndrome in a Tunisian cohort. A total of 120 patients diagnosed with Primary Sjögren’s syndrome and 147 age- and sex-matched healthy controls were genotyped using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method. Statistical analysis revealed a significant association between the miR-499 rs3746444 polymorphism and increased disease risk, with the GG genotype conferring the highest susceptibility (odds ratio [OR] = 9.4, p < 0.001). Conversely, the T allele of the miR-196a2 rs11614913 variant exhibited a protective effect (OR = 0.62, p = 0.018). No statistically significant association was observed for miR-146a rs2910164. These findings underscore the potential involvement of miRNA-related genetic variants in the etiology of Sjögren’s syndrome and highlight the importance of population-specific genetic studies in autoimmune pathogenesis.

Muscle wasting is one of the main causes for exercise intolerance and ventilatory inefficiency in patients with heart failure and a strong predictor of frailty and reduced survival. The prevalence of sarcopenia is at least 20% in patients with heart failure. Patients with heart failure often have subclinical systemic inflammation, which may exert sustained effects on skeletal muscle. Besides exercise, nutrition should also be carefully evaluated as an appropriate diet with selected nutraceuticals may be able to stimulate muscle anabolism and inhibit muscle catabolism. This review summarizes the epidemiological and clinical trial evidence supporting the recommendations for the use of nutraceuticals with anti-inflammatory properties in heart failure and provides an overview of the state of the evidence for nutraceutical supplementation to prevent and/or mitigate heart failure muscle wasting.

Diabetes mellitus is among the diseases with great impact on health and society, not only for its high prevalence but also for its chronic complications and high mortality. This study aimed to estimate the prevalence of type 2 diabetes (T2D) in Tunisia and to evaluate the relationship between this diagnosis, demographics, medical history, physical and blood biochemical measurements and socioeconomic variables. The ATERA-survey was a nationally representative, cross-sectional study conducted between January 2016 and March 2019 using the World Health Organization (WHO) criteria. Data were collected by face-to-face interviews during a door-to-door visit. Diabetes was defined as self-reported history with prescribed glucose-lowering medication or fasting plasma glucose (FPG) ≥ 126 mg/dL (7 mmol/L) or HbA1c level ≥ 6.5% (≥ 48 mmol/mol). Out of an initial recruitment of 11,853 individuals, 10,576 participants (4642 men and 5934 women) aged 25–75 years completed an interview and medical examination. The overall prevalence of T2D obtained from this study was 23.0% [95% confidence interval (CI): 22.2%–23.8%] of which 16.6% were previously known cases of diabetes and 6.4% were newly detected. The prevalence was 23.8% [95% CI: (22.9–24.6)] in men and 22.30% [95% CI: (21.5–23.0)] in women as well as 24.5% and 18.7% in urban and rural residents, respectively. Our results indicate that T2D has become a major public health problem in Tunisia. Urgent measures are needed to prevent diabetes and its related complications.

Background: Obestatin and ghrelin are two gastric hormones that have a potential role in dietary intake regulation. Obestatin/ghrelin ratio has been proposed as activity markers in obesity. The study aimed to evaluate ghrelin, obestatin and the ghrelin/obestatin ratio in obese compared to control subjects and to determine their relationship with anthropometric and metabolic parameters. Methods: Fasting obestatin and ghrelin levels were measured using enzyme-linked immunosorbent assay ELISA in 28 obese and 24 healthy subjects. The fasting ghrelin/obestatin ratio was calculated. Anthropometric and metabolic parameters were also assessed. Results: Obese patients had significantly lower obestatin and ghrelin blood levels compared with controls. The Ghrelin/Obestatin ratio was significantly lower in obese group 0.813±0.0417 ng/ml than in the control group 0.896±0.049 ng/ml, (p<0.001). In obese patients, obestatin and ghrelin were significantly and negatively correlated with BMI and positively correlated with HDL-C. Conclusion: Circulating preprandial ghrelin to obestatin ratio is decreased obese subjects. We suggest that low preprandial ghrelin to obestatin ratio may be involved in the etiology and pathophysiology of obesity.

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. 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. 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 kgm 2 ) (31.4%) and smoking (24.4%). 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.

Objective: To assess the effectiveness of moderate energy restriction for 6 months with reinforcement of household activities, in Tunisian obese women. Design:We conducted a nutritional intervention for 6 months. Participants:We included consecutively 75 volunteer obese women in the "Obesity Unit", Endocrinology Service, La Rabta Hospital, Tunisia; in January 2013. Intervention(s):We prescribed a diet of 1600 Kcal/day; providing 57% of energy as carbohydrate, 30% as fat, and 13% as protein.We advised the reinforcement of the domestic housework activities.Main outcome measure(s): Demographics, lifestyle behaviors, anthropometrics, biologic parameters and dietary intake were assessed at baseline and at 6 months.Analysis: All quantitative variables were reported as the mean ± standard deviation.We used paired-samples t test for comparison of two means and Pearson correlation coefficient (n > 30) to check for correlations.Significance level was set at 0.05.Results: Sixty (80%) women were reviewed at 6 months.There was a significant decrease in body mass index and fat mass and a significant increase of the percentage of lean mass.The total cholesterol, low-density lipoprotein cholesterol, C-reactive protein and leptin levels were reduced at 6 months. Conclusion and implication:The prevention of the cardiovascular complications of the obesity for women of a modest socioeconomic level is achievable through readily accessible means.

Context: 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 (-1 C>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: There were significant differences in the genotype and allele frequencies of CD40 gene -1 C>T (rs1883832) polymorphism between cases and controls. Stratifying according to gender, the association between the TT genotype and MI was statistically significant in males, only. Haplotype analysis revealed that the C-T and T-G haplotypes were associated with an increased risk of MI (p = 0.012 and p < 0.001, respectively). Conclusions: Our work showed a significant association between the -1 C>T (rs1883832) polymorphism of the CD40 gene and MI in the Tunisians.

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 +/- 7.44vs.16.7 +/- 10.6 ng/mL;p < 0.001). Multi-adjusted HR (95% CI) for vitamin D deficiency (25-OHD < 12 ng/mL) was 2.09 (1.27-3.44) for recurrence, 2.63 (1.06-6.49) for progression and 2.93 (1.04-8.25) for mortality in patients with NMIBC. Low plasma 25-OHD in NMIBC patients is associated with higher risk of poor outcome. Future work is required to test whether correction of vitamin D deficiency will improve quality of life and extend survival in these patients.

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.

Purpose: In this study, we investigated the association of two polymorphisms (rs869109213 and rs2070744) in the eNOS gene and one polymorphism BglII in the alpha(2)beta(1) integrin gene (ITGA2) with the risk of diabetic retinopathy (DR) in a Tunisian population. Methods: The study investigated of 110 type 2 diabetes mellitus (T2DM) and 127 DR patients. The genotypes of the eNOS 4b/4a (rs869109213) and -786T/C (rs2070744) polymorphisms and of the BglII polymorphism of ITGA2 were studied using the PCR or PCR-RFLP method. Results: The genotype distributions of the two polymorphisms in eNOS 4b4a and eNOS (-786T/C) were significantly different between T2DM and DR patients (p p = .033, respectively). These polymorphisms were associated with the risk of DR (OR = 2.65, 95%CI [1.45-4.84], p = .002) for the eNOS 4b4a genotype and (OR = 2.43, 95%CI [1.06 - 5.56], p = .036) for the CC genotype of the eNOS gene (-786T/C). Similarly, the genotype distribution of the BglII polymorphism was significantly different between the two groups studied (p = .037). This polymorphism was associated with an increased risk of DR (OR = 4.03, 95% CI [1.17 - 7.85], p = .022) for BglII(+/+). Conclusion: The present study suggests that the polymorphisms 4b4a and -786T/C in the eNOS gene might be associated with DR. In addition, the BglII polymorphism in the ITGA2 gene was a risk factor for DR.

Background: Behcet'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. Methods: 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. Results: 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 (beta, 0.274; p=. 029). Conclusions: 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.

Polymorphisms of paraoxonase gene (PON) cluster have been investigated in numerous studies for their association with myocardial infarction (MI) but the results have been inconsistent. The present study was designed to explore the distribution of PON1, PON2 and PON3 polymorphisms, including genotyping, lipid profile, and PON1 activity, and their association with PON1 activity and MI in a Tunisian population. We conducted a case-control study, including 380 MI cases and 350 controls. Genotyping for PON1, PON2, and PON3 variants was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques. The enzymatic activity of PON1 was measured by a kinetic method using paraoxon as a substrate. We reported that of the 12 genotyped variants two were monomorphic (PON1-R160G and PON3-D107D), and ten showed allelic frequency ≥ 5%. Statistical analyzes identified a protective variant (PON1-824G/A) and four susceptibility variants for the risk of IDM (PON1: Q192R, −108 C/T and 162G/A), PON2-S311C. The study of the lipid profile according to the genotypes revealed that only the S311C variant was associated with apo-B and HDL-c levels. We also reported low activity of PON1 in IDM patients compared to controls. This activity was affected by the Q192R polymorphism, is negatively correlated with age and positively with HDL-c and apo-A1 concentrations. Measurement of the linkage disequilibrium (LD) between pairs of loci revealed that D' varied between (0 and 0.53), whereas the correlation coefficient between alleles r2 varied from (0 to 0.18), reflects low interaction and high recombination between alleles. Analysis of the haplotypes per gene showed that the QLTAAG and RLTGGA combinations were aggravating the risk of MI, while the QLTGAA combination was protective. Our finding suggested that genetic polymorphisms of PON may play a role in the susceptibility to MI among Tunisian population.

Context: Variations in the fat mass and obesity-associated gene (FTO) has been associated with obesity in many populations, but the results are conflicting. Objective: The aim of this study was to evaluate the effect of the rs9939609 polymorphism in the FTO gene on obesity risk and plasma leptin, adiponectin, insulin and lipid concentrations in Tunisians. Materials and methods: Four hundred and ninety-four subjects with obesity and 334 non-obese participated in this study. The rs9939609 (T/A) genotype was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: Significant differences in genotype frequencies were observed between cases and controls. In the separate analysis by gender, the association between the AA genotype and obesity was statistically significant in women but not in men. After stratification by obesity class this association remains only with obesity class III. Discussion: Our study is in agreement with studies on Caucasian, Portuguese and Cebu Filipino populations where a gender-specific association was found between rs9939609 polymorphism and obesity. It is also in agreement with studies on Mexican, Spanish and European populations, where an association was found with obesity class III. Conclusion: The rs9939609 polymorphism of FTO gene is associated with obesity, especially obesity class III in women.

Background/AimAccumulated 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.MethodsA 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.ResultsWe 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.ConclusionCIC haplotype of VEGF gene may be important risk factor for UBC development in Tunisia.

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. 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. 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. The present study found that the ABCB1 G2677 W polymorphism does not affect the lipid-lowering efficacy of atorvastatin.