N. Kaabachi

Metabolic syndrome in Tunisian psoriatic patients: prevalence and determinants.

Background  A significant association between psoriasis and the metabolic syndrome (MetS) has been frequently reported.

Hyperhomocysteinaemia is associated with uveitis but not with deep venous thrombosis in Behçet's disease

Abstract Plasma homocysteine was assessed in Behçets disease (BD) patients in order to determine the prevalence of hyperhomocysteinaemia in BD and to test its association with clinical manifestations of the disease. The study included 59 patients with BD and 118 age- and sex-matched healthy subjects. Plasma homocysteine, vitamin B12 and folate were assessed by automated immunoassay methods. Hyperhomo-cysteinaemia was defined as plasma homocysteine >15μmol/l. Plasma homocysteine concentrations and the prevalence of hyperhomocysteinaemia were significantly higher in BD patients than in controls [median (5th–95th percentile), 11.3 (6.6–28.1) vs. 10.6 (6.6–17.1)μmol/l, and 25.4% vs. 9.3%, respectively]. In BD patients, hyperhomocysteinaemia was related to male gender, disease severity and uveitis [odds ratio (OR), 5.32; 95% confidence interval (CI), 1.43–21.61; p=0.008], but not to age, smoking, disease activity, deep venous thrombosis, arthritis or neurological involvement. The association between uveitis and hyperhomocysteinaemia persisted (multi-adjusted OR, 7.46; 95% CI, 1.03–54.3; p=0.05) after adjusting for gender, age, disease activity and duration, smoking, deep venous thrombosis, and serum concentrations of creatinine, vitamin B12 and folate. Plasma homocysteine should be measured in patients with BD, and the effect of B-vitamin supplementation should be tested in those with hyperhomo-cysteinaemia.

Benzene exposure monitoring of Tunisian workers.

To monitor benzene exposure and to check reliability of urinary trans,trans-Muconic Acid (t,t-MA) as a bio-marker of benzene exposure in local conditions, a study was conducted on 30 Tunisian exposed workers (20 tanker fillers and 10 filling station attendants). The analyses were carried out on environmental air and urinary t,t-MA before (t,t-MAA) and at the end of work shift (t,t-MAB). 20 nonoccupationally exposed subjects were also investigated. The average value of environmental benzene concentration was 0.17 ppm. The differences between t,t-MAA and t,t-MAB concentrations and between t,t-MAB and t,t-MA measured in controls (t,t-MAC) were both significant (p < 0.001). Benzene air concentrations were well correlated with t,t-MAB: R = 0.76. In the nonexposed group, average t,t-MA concentrations is significantly higher among smokers than nonsmokers (P < 0.02). Analysis of urinary t,t-MA offers a relatively simple and suitable method for benzene exposure monitoring.

Hyperhomocysteinemia and End-Stage Renal Disease: Determinants and Association with Cardiovascular Disease in Tunisian Patients

Abstract The study reports on plasma total homocysteine (tHcy) levels in Tunisian patients with chronic renal failure (CRF) and those treated with hemodialysis (HD) and renal transplant (RT). The aims of the study were to identify the determinants of tHcy concentration and to test the association between hyperhomocysteinemia and atherothrombotic disease in end-stage renal disease (ESRD). A total of 35 CRF patients on conservative treatment, 50 HD patients, and 30 RT recipients, and 31 age-and sex-matched healthy subjects were included. Plasma tHcy was assessed by a fluorescent-polarizing immunoassay method. Multivariate analysis was applied to identify the main determinants of tHcy concentration and to assess the relationship between hyperhomocysteinemia and cardiovascular disease. Plasma mean tHcy concentration was significantly increased (p < 0.001) in CRF patients (mean ± SD) (28.9±9.8 μmol/l), in HD patients (29.4±11.1 μmol/l), and in RT (19.3±6.3 μmol/l) patients compared to controls (11.9±4.1 μmol/l). Multivariate analysis using GLM ANOVA modeling demonstrated that tHcy was significantly higher in males (p = 0.02), and was related to age (p = 0.008), albumin (p = 0.005), vitamin B12 (p = 0.002), folate (p = 0.00001), and creatinine clearance (p = 0.0008). However, tHcy was not associated with C-reactive protein and did not significantly differ between CRF, HD, or RT patients. The upper quartile of tHcy concentration was significantly associated with atherothrombotic cardiovascular disease (unadjusted odds ratio (OR) = 3.09; 95% CI, 1.11–8.61; p = 0.01). This association remained significant after adjusting for sex, age, hypertension, and smoking (multi-adjusted OR = 4.78; 95% CI, 1.92–11.9; p = 0.0008). The mean tHcy concentration was 2 to 3 times higher in ESRD patients than in subjects with normal renal function. This increase could be related to glomerular filtration rate reduction and functional B vitamins deficiency, but was not associated with inflammation. The upper quartile of tHcy concentrations confers 4.78-fold increased independent risk for atherothrombotic events in ESRD patients.

Is serum transthyretin a reliable marker of nutritional status in patients with end-stage renal disease?

OBJECTIVE To test the value of serum transthyretin (TTR) concentration as a nutritional marker in renal patients. METHODS The study included 115 renal patients, out of which 35 are on conservative treatment, 50 on hemodialysis and 30 renal transplant recipients, and 31 healthy control subjects. Serum TTR, albumin, transferrin, C-reactive protein (CRP) and alpha1 anti trypsine (AAT) were assessed by immunoturbidimetry, and vitamin A by HPLC. Linear regression models were applied to test the association between serum TTR and body mass index (BMI). RESULTS Serum TTR concentrations were normal, but serum vitamin A, CRP and AAT concentrations were significantly higher in patients. In renal patients, serum TTR was positively and independently related to BMI and was significantly lower in malnourished than well-nourished patients (367+/-91 vs. 417+/-130 mg/L; p=0.05). The risk of serum TTR<300 mg/L was higher in malnourished patients [OR, 4.82 (1.78-13.2); p=0.001]. CONCLUSION Serum TTR concentrations were at normal range in renal patients despite evidence of malnutrition and inflammation. However, they were related to BMI and were significantly lowered in malnourished patients. Thus, serum TTR would reflect nutritional status in renal patients. However, the cutoff of malnutrition should be raised to 300 mg/L.

Predictors for cardiovascular morbidity and overall mortality in Tunisian ESRD patients: A six year prospective study ☆

OBJECTIVES The study was aimed to test the predictive value of several potential cardiovascular factors and markers for non fatal cardiovascular events (CVE) and overall mortality in Tunisian patients with renal failure. SUBJECTS AND METHODS One hundred and fifteen renal failure patients were followed-up from 2000 to 2006. At enrollment, each patient underwent clinical examination and blood collection for analysis of lipid parameters, albumin, C reactive protein (CRP), parathyroid hormone (PTH), homocysteine and hemoglobin. Multivariate Cox regression models were applied to identify the predictors for non fatal CVE and overall mortality. RESULTS During the follow up, seventeen patients were lost. Among the 98 remaining patients, 29 presented a non fatal CVE (21.5%) and 15 were deceased (11.1%). In univariate analyses, non fatal CVE were more frequent in smokers and in patients with high PTH concentrations and low HDL levels. Moreover, low albumin concentrations were univariately associated with overall mortality. In the multivariate analysis, non fatal CVE was significantly and independently associated with age [hazard ratio (95% confidence interval), 1.04 (1.01-1.08); p=0.028] and the upper quartile of PTH concentrations [2.68 (1.24-5.81); p=0.013]. Overall mortality was independently predicted by the bottom quartile of albumin concentrations [5.62 (2.02-15.6); p=0.001] and the upper quartile of CRP concentrations [3.20 (1.14-8.79); p=0.027]. CONCLUSION Advanced age and high PTH levels are the main predictors of CVE, whereas low albumin and high CRP concentrations are the independent predictors of death in Tunisian renal patients. A better control of these factors would greatly increase the patients survival rates.

Polymorphisms of the NOS3 gene in Tunisian patients with Behçet's disease

Behçets 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.

Serum leptin concentration in Tunisian non overweight non obese children

Leptin, an adipocyte-derived peptide hormone, is thought to play a key role in the regulation of body fat mass. Beyond this function, it appears to be an integral component of various hypothalamo-pituitary-endocrine feedback loops. Because childhood and puberty are periods of major metabolic and endocrine changes, we investigated leptin levels in 348 non overweight, non obese children (147 boys, 201 girls, age: 6-12 years) and then correlated these levels with age, anthropometric data, pubertal stage and insulin. A blood sample was collected from each subject to measure leptin and insulin levels by radioimmunoassay. Pubertal stage was assigned by physical examination, according to Tanner criteria for breast development in females and genital development in males. The results showed an increase in leptin levels in an age related way (r = 0.32, p < 0.0001 in girls; r = 0.21, p = 0.011 in boys) following a pattern that paralleled body weight (r = 0.6 in girls; r = 0.56 in boys; p < 0.0001) and BMI (r = 0.59 in girls; r = 0.6 in boys, p < 0.0001), suggesting that body fatness is a regulator of leptin levels in both girls and boys. A significant gender difference (3.39 +/- 2.79 ng/mL in girls vs 1.99 +/- 2.08 ng/mL in boys, p < 0.0001) with an increase during pubertal development in girls was also showed, while the levels remained constant in boys from Tanner stages T1 to T3. A correlation between leptin and insulinemia was noted in girls (r = 0.38, p < 0.0001) but not in boys, suggesting that insulinemia could be a stimulator of leptin synthesis in girls.

FRI0290 Interleukin 10 gene polymorphisms in primary sjÖgren syndrome in a tunisian population

Background Primary Sjögren 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 Sjogrens 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 Sjogrens 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

0139: Detection of myocardial fibrosis in patients with hypertrophic cardiomyopathy evaluated by biological markers

Background Hypertrophic cardiomyopathy (HCM) is a disease characterized by cell disorganization with a matrix remodeling leading to fibrosis. Aim The purpose of our study was to investigate biological markers which are the amino terminal pro peptide of type III collagen (PIIINP), a metalloproteinase (MMP3) involved in the regulation collagen and its specific tissue inhibitor TIPM2. We included 107 patients and 175 controls. We studied the association of serum levels of these markers with clinical, echocardiographic and prognostic parameters. Results In the study population, the mean age was 49 years, 60 were male, 75% were symptomatic (palpitations in 38% of cases, chest pain in 28% of cases, syncope in 25% of cases) the rate of PIIINP was significantly higher in patients compared with controls (361.92±41.6pg/mL vs 242.80±46.7ng/ml; p=0.036). Same for themmP3 and TIMP2 levels (12.16±4.3pg/mL vs 10.4±3.78pg/mL and 63.4±23.5pg/mL vs 57.50±21.43pg/mL, respectively, p=0.03). We note that themmP3 / TIMP2 ratio is correlated to left ventricular (LV) mass and the left atrium volume (r=0.560, p=0.002, and r=0.633, p=0.001 rspectively), the PIIINP is correlates to the maximum thickness of the LV (r=0.466, p=0.002), to the global longitudinal Strain of the LV and its mass (r=0.578, r=0.001 and r=0.490, p=0.003 respectively). Patients with a history of syncope and episodes of non-sustained ventricular tachycardia, were younger and had a significantly higher rate of PIIINP (432.5±34.6pg/mL vs 320.44±32.8pg/mL, p=0.002) and less LV GLS (-14.7±2.6% vs 16.7±3.2%, p=0.0034). Conclusion HCM is characterized by ventricular and atrial remodeling and fibrosis related to the collagen accumulation that is reflected bymmP3/ TIMP2 ratio serum and the PIIINP concentration. These parameters were correlated with LV function may represent potential risk factors for the ventricular dysrhythmia and LV dysfunction.