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

Behçet'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.

Prehypertension among adults in Great Tunis region (Tunisia): A population-based study.

PURPOSE: The present study aimed to determine the prevalence of prehypertension (preHTN) and its cardiometabolic profile in Tunisians, and to estimate the risk for coronary heart disease (CHD) according to blood pressure status. PATIENTS AND METHOD: This cross-sectional study was conducted in 2004-2005, and used a two-stage cluster sampling method to select a representative sample of the Great Tunis population. A total of 2712 individuals (1228 men and 1484 women), aged 35 to 69 years were included. Definition and classification of hypertension (HTN) was performed according to guidelines from the Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure (JNC-7) report. RESULTS: The prevalence of preHTN and HTN was 56.8% and 25.0% in males, and 43.1% and 36.1% in females, respectively. Subjects with preHTN and those with HTN showed higher prevalence of diabetes, dyslipidemia, obesity and abdominal obesity than the normotensive (NT) group. The metabolic syndrome (MetS) was found in 8.0%, 17.8% and 53.8% of NT, preHT and HTN subjects, respectively. The risk of developing CHD within 10 years, as predicted by the Framingham-Anderson model, was above 15% for 3.9%, 31.1% and 65.0% among NT, preHTN and HTN subjects, respectively. In multivariate analysis, preHTN was associated with age (OR [95% CI], 1.02 [1.01-1.03]; P<0.01), male gender (2.51 [1.89-3.23]; P<0.001), obesity (2.36 [1.71-3.26]; P<0.01), abdominal obesity (1.53 [1.14-2.06]; P<0.01) and smoking (0.70 [0.53-0.92]; P<0.01). CONCLUSION: PreHTN is very common in Tunisians. It is associated with a higher prevalence of cardiometabolic risk factors and confers a higher risk for subsequent CHD. These findings support the recommendations of lifestyle modification for preHTN patients.

Plasma fatty acids profile and estimated elongase and desaturases activities in Tunisian patients with the metabolic syndrome.

This study aimed to determine plasma fatty acids pattern and to estimate desaturases activities in Tunisian subjects with metabolic syndrome (MetS). A total of 1975 adults were randomly selected from the Great Tunis region (Tunisia). MetS was defined according to the International Diabetes Federation criteria. Saturated and monounsaturated fatty acids levels and delta 9 desaturase activity were increased, but polyunsaturated fatty acids (PUFA) levels and delta 5 desaturase activity were decreased in patients with MetS. Using multivariate analysis, MetS was found inversely associated with PUFA; compared to first quartile, multi-adjusted odd ratios (95% confidence interval) of MetS were 0.80 (0.54-1.17), 0.47 (0.27-0.81) and 0.32 (0.15-0.68) for second, third and fourth quartiles of PUFA, respectively. Altered fatty acids pattern in MetS is likely related to both dietary and metabolic changes.

The G3057A LEPR polymorphism is associated with obesity in Tunisian women.

OBJECTIVES: The aim of this study was to evaluate the effect of the G3057A (rs62589000) LEPR polymorphism on obesity risk and plasma leptin, insulin, and lipid levels in a sample of the Tunisian population. DESIGN AND METHODS: Three hundred and ninety-three obese patients and 317 controls participated in this study. The G3057A genotype was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: In the entire study sample, no significant differences in genotype frequencies were observed between obese patients and controls. However, stratified analysis by gender revealed a quantitative increase in the variant allele (33.3% vs. 25.8%; χ(2)=4.90, p=0.026) in obese women (but not men) compared to controls. When a dominant model of inheritance was assumed, the GA+AA genotypes were more prevalent in these obese female patients than in controls (58.3% vs. 47.8%; χ(2)=4.08, p=0.044). Unconditional logistic regression showed that in women only, obesity risk was significantly higher for homozygotes for the variant allele (OR=2.73, 95% CI 1.03-7.21) and for carriers of GA+AA genotypes (OR=1.53, 95% CI 1.01-2.31) compared with homozygotes for the normal allele. The association between the G3057A LEPR variant and obesity remained statistically significant even after adjustment for age. No relationship was found between the G3057A LEPR polymorphism and leptin and insulin levels. Additionally, this LEPR gene variant had no effect on plasma lipid concentrations. CONCLUSION: There is evidence in this study that the G3057A LEPR polymorphism is associated with obesity in Tunisian women.

Polyunsaturated fatty acids deficits are associated with psychotic state and negative symptoms in patients with schizophrenia.

The study was aimed to examine membrane polyunsaturated fatty acids (PUFAs) profile in patients with schizophrenia (SZ) before and after antipsychotic medication and test their association with psychopathology. Erythrocyte membrane fatty acids were analysed by gas chromatography in 36 drug-free patients with SZ and 36 controls. Psychometric evaluation and blood sampling were achieved at baseline and after 3 months of antipsychotic treatment. At enrolment, levels of total PUFAs and arachidonic (AA) and docosahexaenoic (DHA) acids were significantly lower, but ω6/ω3 PUFAs ratio was higher in patients. AA and DHA were negatively related to the Andreason's scale for assessment of negative symptoms (SANS) score. DHA was inversely related to "alogia", "anhedonia", "avolition", and "blunted affect" subitems of SANS. After 3 months under typical antipsychotic drugs, fatty acid profile turned into comparable to controls in parallel with psychopathology improvement. Data indicate that PUFAs deficits are associated with psychotic state and negative symptoms of SZ.

Lack of association between monocyte protein-1 (MCP-1) -2518 A>G chemoattractant and C-C chemokine receptor 2 (CCR2) Val64Ile polymorphisms and multiple sclerosis in a 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.

The metabolic syndrome: prevalence, main characteristics and association with socio-economic status in adults living in Great Tunis.

AIMS: This study aimed to determine the prevalence of the metabolic syndrome (MetS) and its association with socio-economic status in the population of Great Tunis. METHODS: The study included 2712 subjects (1228 men and 1484 women), aged 35-70 years and living in the Great Tunis region, all of whom were recruited between March 2004 and June 2005. The sample was weighted by using the inverse of the response rate according to governorate, district and gender. The MetS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III. RESULTS: In the studied population, the overall prevalence of the MetS was 31.2%, and it was significantly more frequently seen in women than in men (37.3% vs 23.9%, respectively; P<0.001), as were abdominal obesity (69% vs 21.6%, respectively; P<0.001), high blood pressure (50.3% vs 43.1%, respectively; P<0.001) and low HDL cholesterol (40.6% vs 33.6%, respectively; P<0.001), the most common characteristics of the MetS. Also, the prevalence of the MetS increased with age in both genders, but more so in women. In those aged greater than 55 years, the prevalence of MetS was 56.7% in women and 30.7% in men. An inverse relationship was observed between level of education and prevalence of the MetS in women, with the highest prevalence being in illiterate women and the lowest in those who were university graduates. CONCLUSION: The prevalence of the MetS is markedly high within the population of Great Tunis and especially in women. As these findings predict future increases in cardiovascular disease in these populations, substantial efforts need to be made to fight against obesity and sedentary lifestyles to ameliorate the expected poor health outcomes.

[Prevalence of conventional cardiovascular risk factors in the Great Tunis population]. / Prévalence des facteurs de risque cardiovasculaires conventionnels dans la population du Grand Tunis.

BACKGROUND: This study was designed to determine the prevalence of main cardiovascular risk factors in the population of Great Tunis. SUBJECTS AND METHODS: This cross-sectional study included 2483 individuals aged 35 to 70 years dwelling in the Great Tunis region, recruited between March 2004 and June 2005. The sample was weighted using the inverse of response rate according to governorate, district and sex. RESULTS: Obesity and abdominal obesity were observed respectively in 34 and 48% of subjects. The prevalence of these two factors was particularly elevated in females (46 and 69% respectively). Hypertension was common (31%), especially in women (36%). Diabetes mellitus and dyslipemia were found in 15 and 21% of subjects, respectively, without difference according to sex. More than half of men and 8% of women were current smokers. CONCLUSION: The prevalence of conventional cardiovascular risk factors is dramatically high in the population of Great Tunis. These findings predict a future expansion of cardiovascular diseases in this population. Profound changes of lifestyle and dietary habits of Tunisians are needed to reduce the risk of cardiovascular morbidity and mortality.

The -2548G/A LEP polymorphism is associated with blood pressure in Tunisian obese patients.

OBJECTIVE: 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. DESIGN AND METHODS: 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. RESULTS: 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 (p<0.001) 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). CONCLUSION: The present study showed that the -2548G/A LEP polymorphism is associated with blood pressure in obese male patients.

[Distribution of cardiovascular risk factors in coronary patients in Sahel, Tunisia]. / Distribution des facteurs de risque cardio-vasculaire chez des patients coronariens dans le Sahel tunisien.

We evaluated cardiovascular risk factors and their association in patients in Sahel, hospitalized for coronary disease over the period 1994-1998. The clinical features of 3455 patients (72.4% men, 1741 with myocardial infarction, 1714 with unstable angina) were analysed on hospital admission. The prevalence of smoking, dyslipidaemia, hypertension, diabetes and obesity was 77.4%, 39.4%, 28.5%, 42.5% and 25.1% respectively in men and 2.9%, 43.7%, 59.2%, 56.6% and 31.9% respectively in women. With this risk factor profile a national strategy of primary prevention and heart health promotion is needed in Tunisia.

[XbaI polymorphism of apolipoprotein B gene in a Tunisian population: alleles frequencies and relationship with plasma lipid parameters]. / Polymorphisme XbaI du gène de l'apolipoprotéine B dans une population tunisienne: fréquences alléliques et relation avec les paramètres lipidiques plasmatiques.

Apolipoprotein B (Apo B) is a component of chylomicrons, low-density lipoproteins (LDL), very low density lipoproteins (VLDL), and intermediate-density lipoproteins (IDL) and is the ligand for the LDL receptor. Thereby, Apo B plays a central role in lipoprotein metabolism and in maintaining the normal homeostasis of serum cholesterol levels. Several Apo B restriction fragment length polymorphisms (XbaI, EcoRI, MspI) have been reported to be associated with variation in lipid levels, obesity and/or coronary artery disease. To date, no data are available on relationship between XbaI Apo B polymorphism and lipid levels in Tunisian population. Here, we report frequencies of the XbaI polymorphism of the Apo B gene and we assess the effect of this polymorphism on lipid and lipoprotein concentrations in Tunisian population. Blood samples from 296 Tunisian individuals (112 women and 184 men, aged 51.4+/-9.6 years), were analysed for total cholesterol, triglycerides, HDL-cholesterol and apolipoproteins A1 and B. In parallel, genotyping by means of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was performed. The XbaI polymorphism was associated with differences in plasma cholesterol (p=0.04), triglyceride (p=0.02) and apolipoprotein A1 (p=0.004), individuals with the genotype X1X1 have the lowest mean levels and those with the genotype X2X2 have the highest, with the individuals heterozygous for the polymorphism having intermediate levels. According to sex, the XbaI polymorphism effect was only observed for triglyceride in men. Thus, the results demonstrate an influence of XbaI polymorphism of Apo B gene on serum total-cholesterol, triglycerides and apolipoprotein A1 concentrations among Tunisian population.

Apolipoprotein B signal peptide polymorphism: distribution and influence on lipid parameters in Tunisian population.

Apolipoprotein B (apo B) is the major protein component of LDL, VLDL and chylomicrons. Numerous polymorphisms of the apolipoprotein B gene have been described. Particularly, the insertion/deletion polymorphism located in the coding part of the signal peptide of apo B, associated with modification of lipid concentrations and the risk of cardiovascular disease, has been reported in the general population. No such study in the Tunisian population has been performed. The aim of our study was to assess the effect of insertion/deletion polymorphism of the apolipoprotein B gene on lipid levels in a sample of the Tunisian population. A total of 458 unrelated subjects (321 men and 137 women) were included. The insertion/deletion polymorphism was determined by electrophoresis on polyacrylamide gels after PCR amplification. The relative frequencies of the Ins and Del alleles were 0.74 and 0.26, respectively. These frequencies were similar to those found in other Caucasian populations. There was no significant difference in serum TC, TG, and HDL-C levels due to the influence of the genotypes. However, significant variation among the three genotypes was seen for LDL-cholesterol (p<0.001) and apo B (p<0.001) levels. Individuals homozygous for the Del allele had higher levels than individuals homozygous for the Ins allele, while individuals heterozygous for both alleles exhibited intermediate levels. When the data were analyzed in men and women separately, a similar effect was seen in both groups. Our results show that distribution of apo B insertion/deletion polymorphism in Tunisians is similar to other Caucasian population and confirm the reported association with serum LDL-cholesterol and apo B concentrations.

[Distribution of cardiovascular risk factors in coronary patients in Sahel Tunisia]

We evaluated cardiovascular risk factors and their association in patients in Sahel, hospitalized for coronary disease over the period 1994-1998. The clinical features of 3455 patients [72.4% men, 1741 with myocardial infarction, 1714 with unstable angina] were analysed on hospital admission. The prevalence of smoking, dyslipidaemia, hypertension, diabetes and obesity was 77.4%, 39.4%, 28.5%, 42.5% and 25.1% respectively in men and 2.9%, 43.7%, 59.2%, 56.6% and 31.9% respectively in women. With this risk factor profile a national strategy of primary prevention and heart health promotion is needed in Tunisia

Apolipoprotein E polymorphism in the Tunisian population: frequency and effect on lipid parameters.

OBJECTIVES: 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. DESIGN AND METHODS: Apo E polymorphism was investigated using PCR, and plasma lipid parameters were measured in 122 men and 111 women aged 35 to 87 years. RESULTS: The allele frequencies were epsilon2: 7.3%, epsilon3: 84.6%, and epsilon4: 8.1%. Apo E polymorphism was associated with significant differences (P<0.001) 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 (BMI>30 kg/m2), TG concentrations were significantly lower in individuals homozygous for the epsilon3 allele compared to those with the alleles epsilon2 or epsilon4. CONCLUSION: 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.

Apolipoprotein B signal peptide polymorphism and plasma LDL-cholesterol response to low-calorie diet.

OBJECTIVE: To assess the effect of the apolipoprotein B Ins/Del signal peptide. Polymorphism on plasma lipid levels in overweight subjects before and after a low-calorie diet. DESIGN: Diet intervention study (25% reduction in energy intake during 2.5 months) in relation to genetic factors. SUBJECTS: A total of 231 unrelated patients (146 women/85 men) recruited on the basis of body mass index (BMI)> or =25 kg/m(2). MEASUREMENTS: BMI, waist to hip ratio, blood lipids and lipoproteins, at entry and after 2.5 months, determination of apo B Ins/Del genotypes. RESULTS: On spontaneous diet, subjects carrying the Del allele had higher LDL-cholesterol (Del/Del: 3.97+/-0.62 mmol/l; Ins/Del: 3.87+/-1.01 mmol/l; Ins/Ins: 3.61+/-0.88 mmol/l) (P=0.038). When submitted to low-calorie diet, subjects with Del/Del genotypes reduced their LDL-cholesterol (-16.8%) more than subjects with Ins/Del or Ins/Ins (-4.7% and +0.9%, respectively) (P=0.001). CONCLUSION: In overweight or obese people, the response of plasma LDL-cholesterol levels to low-calorie diet is modulated by genetic variation at the apo B locus. Overweight subjects with the Del allele of the apo B signal peptide polymorphism are predisposed to high LDL cholesterol levels but their LDL cholesterol responds well to diet. These results demonstrate the importance of the interaction between genes and nutritional environment in the determination of the lipid levels.

[Distribution of cardiovascular risk factors in a Tunisian cohort of 6901 coronary patients]. / Distribution des facteurs de risque cardiovasculaire chez une cohorte tunisienne de 6901 coronariens.

The Tunisian epidemiological data on cardiovascular disease in the hospital environment are scarce. The aim of this study was to evaluate the frequency of cardiovascular risk factors and their association in patients hospitalised for coronary disease in coronary care units at Rabta, Charles Nicolle, Habib Thameur and Military hospitals, Tunis, over the period 1994-1998. The clinical features of 6901 patients (75.7% men, 3760 myocardial infarction, 3141 unstable angina) on hospital admission were analysed. The prevalence of smoking, dyslipidemia, hypertension, diabetes and obesity was 86; 49.8; 33.9; 40.7 and 15.2% respectively in the men and 12.9; 52.4; 64.6; 53.4 and 29.8% respectively in women. With this risk factor profile Tunisia has to implement a national strategy of primary prevention and heart health promotion in addition to the efforts recently made in secondary prevention of some chronic disease such as hypertension, diabetes and smoking.

[Polymorphism insertion/deletion of apolipoprotein B gene: effect on lipid levels in obese patients]. / Polymorphisme insertion/délétion du gène de l'apolipoprotéine B: effet sur les concentrations lipidiques chez les sujets obèses.

Apolipoprotein B (apoB) is the major proteic component of LDL, VLDL and chylomicrons. Numerous polymorphisms of the apolipoprotein B gene have been described. Particularly, a polymorphism of insertion/deletion located in the coding part of the signal peptide of apoB, associated with modifications of lipid concentrations and the risk of cardiovascular disease, has been reported in the general population. Since obesity is frequently associated with dyslipidemias, the aim of our study was to assess the effect of the insertion/deletion polymorphism of the apolipoprotein B gene on lipid levels in obese subjects. 234 unrelated caucasian obese subjects (74 men and 160 women, aged 39.3 +/- 10.5, BMI : 32.8 +/- 4.7) were recruited. The insertion/deletion polymorphism was determined by electrophoresis in polyacrylamide gels after PCR amplification. The relative frequencies of the Ins and Del alleles were 0.71 and 0.29 respectively. These frequencies were similar to those found in other Caucasian populations. In the whole population, individuals with the Del/Del genotype had significantly higher total-cholesterol to HDL-cholesterol ratios (p = 0.004), LDL-cholesterol to HDL-cholesterol ratios (p = 0.01) and TG-VLDL levels (p < 0.05). They also showed a tendency for higher triglyceride levels (p = 0.09) and lower HDL-cholesterol, apolipoprotein AI and LpAI levels. The allele deletion results in the absence of three amino acids (Leu-Ala-Leu) in the signal peptide of apo B. In the obese people, these structural changes may have some effect on lipid metabolism and cause variation in serum lipid concentrations.

[VNTR3' polymorphism of apoliproprotein B gene in obese people]. / Polymorphisme VNTR3' du géne de l'apolipoprotéine B chez les sujets obèses.

Apolipoprotein B (apo B) is the major component of LDL, VLDL and chylomicrons. Variations of lipid concentrations in obese people result from obesity, nutritional and genetic factors. Many genetic polymorphisms of the apo B have been described, associated with variation of lipid concentrations. The aim of the present study was to assess the effect of VNTR3' polymorphism of the apoB gene on lipid and lipoprotein concentrations in overweight subjects. 234 unrelated outpatients (160 women and 74 men, aged 39.3 y 10.5; BMI: 32.8 kg/m2 4.7) were recruited. Using the polymerase chain reaction followed by electrophoresis in polyacrylamide gels, 15 different alleles have been identified. Among them four have been observed less than 5 times in our study. Alleles with 21, 25, 35 and 42 repeats have been observed once. The most frequent is VNTR36 allele (38%), followed by alleles 34, 30, 48, and 46 repeats whose frequencies are 20, 9, 8, and 7% respectively. The possible association between alleles of the VNTR3' of the apoB and anthroprometric and lipid variables was examined. Subjects with 50 repeat allele had significantly higher BMI, and subjects with 32 repeat allele had significantly higher HDL-C and ApoAI levels. Our study confirms in the obese subjects, results published in the general litterature, and shows that the apoB has an important role in the metabolism of plasma lipids and most particulary its gene variants.