Association of MTHFR C677T, MTHFR A1298C, and MTRR A66G Polymorphisms with Neural Tube Defects in Tunisian Parents.

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.

Associations of rs1883832 and rs4810485 polymorphisms of CD40 gene with myocardial infarction in the Tunisian population.

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.

Association of systemic beta-defensin-1 and -20G/A DEFB1 gene polymorphism with Behçet's disease.

BACKGROUND: 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. 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 ±â€¯3.52 ng/mL vs. 5.30 ±â€¯3.02 ng/mL; p < .001), and in BD patients with neurological involvement than those without (11.1 ±â€¯4.12 ng/mL vs. 9.19 ±â€¯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 (ß, 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.

Decreased Oleic Acid and Marine n - 3 Polyunsaturated Fatty Acids in Tunisian Patients with Urothelial Bladder Cancer.

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.

The rs9939609 polymorphism in the fat mass and obesity associated (FTO) gene is associated with obesity in 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.

Haplotype-based association of Vascular Endothelial Growth Factor gene polymorphisms with urothelial bladder cancer risk in Tunisian population.

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.

Lack of association between FokI polymorphism in vitamin D receptor gene (VDR) & type 2 diabetes mellitus in the Tunisian population.

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.

Association Between the G20210A Polymorphism of Prothrombin Gene and Myocardial Infarction in Tunisian 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.

Alpha Adducin G460T Variant is a Risk Factor for Hypertension in Tunisian Population.

BACKGROUND: Adducin is a membrane cytoskeletal protein, consisting of three subunits: α, ß, 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.

Bladder Cancer is Associated with Low Plasma 25-hydroxyvitamin D Concentrations in 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 <30 nmol/L and 30 to 49.99 nmol/L, respectively. Logistic regression models adjusting for gender, age, smoking status, duration of smoking, occupational exposure, and season were applied. Vitamin D deficiency (50.4% vs. 34.8%; P < 0.001) and insufficiency (40.4% vs. 26.8%; P < 0.001) were more frequent in patients than controls. Multivariate analysis showed that UBC is associated with vitamin D deficiency [odd-ratio (95% confidence interval), 3.71 (1.76-7.80); P = 0.001] and vitamin D insufficiency [2.65 (1.40-5.01); P = 0.003]. Other predictors of UBC were female gender, tobacco use, smoking duration, and occupational exposure. Plasma 25-OHD concentrations are low in Tunisian patients with UBC. These findings support experimental and epidemiological evidence of protective role of vitamin D against UBC but could not ascertain causal relationship. Further prospective studies and clinical trials are warranted to check causality.

The Gly482Ser polymorphism of the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is associated with type 2 diabetes in Tunisian population.

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.

Plasma total homocysteine: usual values and main determinants in adults living in the Great Tunis region.

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.

Tumor necrosis factor-α (TNF-α) -863C/A promoter polymorphism is associated with type 2 diabetes in Tunisian 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.

Polymorphisms of the NOS3 gene and risk of myocardial infarction 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 -786T>C (rs2070744), 894G>T (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 894G>T and -786T>C single nucleotide polymorphisms were analyzed by PCR-RFLP, and 4a4b polymorphism just for PCR. There was significant linkage disequilibrium between the three NOS3 polymorphisms (p<0.0001). The genotype distribution and allele frequency of NOS3 4a4b, but not -786T>C and 894G>T, 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.

G protein beta3 subunit gene C825T and angiotensin converting enzyme gene insertion/deletion polymorphisms in hypertensive Tunisian population.

BACKGROUND: We investigated the interaction between the G protein beta3 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.

Lack of association between C3123A polymorphism of the angiotensin II type 2 receptor gene and hypertension in Tunisian population.

BACKGROUND: Hypertension is a polygenic disease. Various singlenucleotide gene polymorphisms of renin angiotensin system have been explored in hypertension. Angiotensin II, the major biologically active component of this system, exerts its effect via two pharmacologically distinct subtypes of angiotensin II receptors, the angiotensin II type 1 receptor and the angiotensin II type 2 receptor. AIM: To examine whether the 3123 C/A polymorphism of angiotensin II type 2 receptor gene is involved in hypertension in a sample of Tunisian population. METHODS: Atotal of 403 normotensive subjects and 382 hypertensive patients were included in the study. Genotyping was performed by polymerase chain reaction followed by Alu I restriction digestion. RESULTS: The frequency of "A" genotype was not significantly different between the two groups in men (¯2=1.18; p=0.16). The estimated odds prevalence for hypertension ("A" versus "C") was 0.77 (95% CI 0.49 to 1.22, p=0.27). After adjustment for confounding factors, the OR for hypertension remained no significant (OR: 1.49, 95% CI: 0.84-2.63, p=0.16). In women, genotype distributions for C3123A variant in hypertensive patients were not significantly different from normotensive subjects (¯2=3.16; p=0.20). Multiple logistic regression analysis showed that the AA genotype was not significantly associated with hypertension (OR: 1.09, 95% CI: 0.58-2.06, p=0.77). CONCLUSION: In the present study, we showed that the 3123 C/A polymorphism of AGT2R gene is not a significant factor for hypertension in a sample of Tunisian population.

Dyslipidemia in the Greater Tunis population: prevalence and determinants.

BACKGROUND: Economic development and socio-demographic changes have led to increased frequency of cardiovascular disease and other chronic diseases in Tunisia. OBJECTIVES: To assess the prevalence of different types of dyslipidemia and to examine their association with sociodemographic characteristics in the Greater Tunis population. METHODS: The study included 2712 subjects (1228 men and 1484 women) aged 35-70 years, recruited during the years 2004 and 2005 from the Greater Tunis population. Hypercholesterolemia, hypertriglyceridemia, and low HDL cholesterol were defined according to the National Cholesterol Education Program-Adult Treatment Panel III. RESULTS: The prevalence of hypercholesterolemia, hypertriglyceridemia, and low HDL cholesterol was 40.8% (34.9% in males and 45.8% in females; p < 0.001), 29.2% (31.1% in males and 27.6% in females; p < 0.05), and 21.2% (32.5% in males and 11.5% in females; p < 0.001), respectively. The prevalence was higher in urban than rural regions. Hypercholesterolemia was more frequent in illiterate women and in men with high education level. CONCLUSIONS: Dyslipidemias are common in Tunisians, mainly in urban areas, in illiterate women as well as in men with high levels of education. Profound changes of life style and dietary habits of Tunisians are needed to reduce the risk of cardiovascular diseases.

Association between endothelial nitric oxide gene intron 4a4b VNTR polymorphism and plasma homocysteine concentrations in Tunisian male patients with myocardial infarction.

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<.001). However, no significant difference was observed for tHcy concentrations in the control group. In conclusion, the NOS34a4b gene polymorphism (presence of 4a allele) is associated with MI and influences plasma tHcy concentrations in patients with MI in the Tunisian male population.

Polymorphisms in the CC-chemokine receptor-2 (CCR2) and -5 (CCR5) genes and risk of myocardial infarction among Tunisian male patients.

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<0.001) and 64Ile-Ins haplotype (12.3% vs. 16.7%, OR=0.58, 95% CI=0.42-0.80, p<0.001). CONCLUSION: A protective effect of the CCR5-Δ32 polymorphism against MI in the Tunisian population was found.

Adiponectin and metabolic syndrome in a Tunisian population.

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.