Haifa Sanhaji

Association between the − 2518G/A polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene and myocardial infarction in Tunisian patients

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.

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.

Phenylketonuria is still a major cause of mental retardation in Tunisia despite the possibility of treatment

BACKGROUND AND OBJECTIVE Accumulation of phenylalanine following a deficiency of phenylalanine hydroxylase activity generates a brain damage with mental retardation: phenylketonuria (PKU). In the developing countries, where PKU systematic neonatal screening program is not established yet, the management of PKU handicap is not properly carried out. The aim of this study was to estimate the frequency of the PKU diagnosed following clinical features anomalies, to provide information about the untreated PKU patients profile in Tunisia not covered by neonatal screening. Also it is stressed that treated patients have a normal development. PATIENTS AND METHODS This is a retrospective study of 156 cases of PKU detected in Tunisia over 20 years following symptoms suggestive of inherited metabolic disease. Phenylalaninemia level was performed by fluorometric method. Among them 9 patients were treated. RESULTS The PKU estimated frequency was 1/7631. The diagnosis mean age was 4 years. The phenylalaninemia mean was 1680 μmol/L; the classical PKU form accounted for 85.3% of cases and the dominant clinical symptoms were: mental retardation (88.2%), motor delays (87.7%), speech difficulties (83.2%) and pigmentation anomalies (61.7%). The treated patients responded to treatment and showed a normal development. CONCLUSION The establishment of neonatal screening should be a priority to avoid cases of mentally retardation.

The paraoxonase L55M and Q192R gene polymorphisms and myocardial infarction in a Tunisian population.

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.

Association of a 27-bp repeat polymorphism in intron 4 of endothelial constitutive nitric oxide synthase gene with hypertension in a Tunisian population.

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 (chi(2)=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; chi(2)=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.

Association between the −2518G/A polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene and hypertension in Tunisian patients

OBJECTIVES Monocyte chemoattractant protein-1 (MCP-1:CCL2) has been demonstrated to be involved in the pathophysiology of atherosclerosis and hypertension. This study was aimed to investigate whether the single nucleotide polymorphism (SNP) at -2518 of the MCP-1 gene promoter region is associated to hypertension in a sample of Tunisian population. DESIGN AND METHODS A total of 290 Tunisian patients with hypertension and 390 normotensive 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 A significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with hypertension had a frequency of 7.2% for the GG genotype, 35.2% for the AG genotype and 57.6% for the AA genotype. Normotensive subjects had a frequency of 3.6% for the GG genotype, 29.7% for the AG genotype and 66.7% for the AA genotype (chi(2)=8.02, p=0.01). The hypertension patient group showed a significant higher frequency of the G allele compared to the controls [0.24 vs. 0.18; OR (95%CI), 1.46 (1.11-1.91), p=0.004]. The association between the -2518 G/A polymorphism of MCP-1 gene and hypertension remained significant after adjustment for other well-established cardiovascular risk factors. CONCLUSION The present study showed a significant and independent association between the -2518G/A polymorphism of the MCP-1 gene (presence of G allele) and hypertension in the Tunisian population.

Association between -786TC polymorphism in the endothelial nitric oxide synthase gene and hypertension in the Tunisian population

BACKGROUND Nitric oxide (NO) is produced by endothelial cells and serves as a potent vasodilator. Several lines of evidence have shown that NO plays an important role in the regulation of blood pressure and regional blood flow. Recent genetic studies have shown an association between the -786TC polymorphism in the endothelial nitric oxide synthase gene (NOS3) and coronary artery diseases, but any possible association with hypertension has been controversial. In the present study, we examined a possible association between the -786TC polymorphism of the NOS3 gene and hypertension in a sample of the Tunisian population. METHODS A total of 288 unrelated Tunisian patients with hypertension and 373 normotensive subjects were included in the study. The -786TC gene polymorphism was analyzed by PCR-RFLP. RESULTS A significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with hypertension had a frequency of 19.7% for CC genotype, 52.9% for TC genotype and 27.3% for TT genotype. The control had a frequency of 14.7% for the CC genotype, 47.2% for the TC genotype and 38.1% for the TT genotype (χ²=9.09, p=0.01). The hypertension patient group showed a significant higher frequency of the C allele compared to the controls (0.46 vs. 0.38; χ²=8.26, p=0.004). The odds ratio of hypertension for C vs. T allele frequencies was statistically significant 1.59 (1.14-2.21) at 95% CI, p = 0.004 in men, whereas it was non-significant in women 1.21 (0.87-1.67), p=0.23. CONCLUSION The present study showed a significant and independent association between the -786TC gene polymorphism (presence of C allele) and hypertension in the Tunisian population.

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.

Association of rs2781666 G/T polymorphism of arginase I gene with myocardial infarction in Tunisian male population

OBJECTIVES The aim of this study was to investigate the association between rs2781666 G/T polymorphism of arginase I (ARG I) gene and myocardial infarction (MI) in the Tunisian male population. DESIGN AND METHODS Three hundred eighteen patients with MI and 282 controls were recruited. The rs2781666 G/T polymorphism of ARG I was determined by PCR-RFLP analysis. RESULTS Patients had significantly higher frequency of TT genotype compared to controls (10.4% vs. 6.7%; p<0.001). The MI patients showed higher frequency of T allele compared to the controls [0.33 vs. 0.22; OR (95% CI), 1.79 (1.37-2.34), p<0.001]. The association between rs2781666 G/T polymorphism of ARG I gene and MI remained significant after adjustment for other well-established risk factors. CONCLUSION A significant association between rs2781666 G/T polymorphism of ARG I gene and MI was found in the Tunisian male population.

Founder effect confirmation of c.241A>G mutation in the L2HGDH gene and characterization of oxidative stress parameters in six Tunisian families with L-2-hydroxyglutaric aciduria

L-2-hydroxyglutaric aciduria (L2HGA) is an autosomal recessive neurometabolic disorder characterized essentially by the presence of elevated levels of L-2-hydroxyglutaric acid (LGA) in plasma, cerebrospinal fluid and urine. L2HGA is caused by a deficiency in the L2-Hydroxyglutaric dehydrogenase (L2HGDH) enzyme involved in the oxidation of LGA to the alpha 2-ketoglutarate. LGA has been proposed as an endo- and exogenous cytotoxic organic acid that induces free radical formation and generation of reactive oxygen species (ROS). In this report, we analyzed 14 L2HGA patients belonging to six unrelated consanguineous families the south of Tunisia. The patients were diagnosed with L2HGA disease confirmed on the presence of high level of LGA in urine. We analyzed the L2HGDH gene in all probands and identified the same c.241A>G homozygous mutation, which was previously reported in Tunisia. We also used intragenic single nucleotide length polymorphisms (SNPs) and two extragenic microsatellites flanking the L2HGDH gene to confirm the founder effect of c.241A>G mutation in the 14 studied cases. In addition, we carried out the measurement of the oxidative stress parameters in the plasma of L2HGA patients which revealed a significant increase in the malondialdehyde levels (MDA), a biomarker of lipid peroxydation, and the reduced glutathione (GSH). A diminution of the antioxidant enzyme activities including superoxide dismutase (SOD), glutathione peroxidase (GPx), was also observed.