Postmenopausal hypertension, abdominal obesity, apolipoprotein and insulin resistance.

This study aimed to evaluate the association of abdominal obesity, apolipoprotein and insulin resistance (IR) with the risk of hypertension in postmenopausal women. We analyzed a total of 242 women aged between 35 and 70 years. Blood pressure (BP), anthropometric indices, lipid profile, fasting glucose, insulin, C-reactive protein (CRP) and apolipoprotein concentrations were measured. Homeostasis model assessment (HOMA) was used to assess IR. Hypertension was defined as a systolic BP (SBP) ≥140 mmHg and/or diastolic BP (DBP) ≥90 mmHg or current treatment with antihypertensive drugs. Women with hypertension showed significantly higher mean values of age, SBP and DBP, waist circumference (WC), fasting plasma glucose (FPG), insulin, HOMAIR and the apolipoprotein B (apoB). When analyses were done according to the menopausal status, higher prevalence of hypertension was observed in postmenopausal women (72.8% vs. 26.0%, p < 0.001) compared to their premenopausal counterparts. Postmenopausal women showed also significantly higher mean values of SBP and DBP, WC, HOMAIR and apoB. Multivariate linear regression analysis revealed that SBP was significantly affected by WC (p = 0.034), apoB (p = 0.038) and log HOMAIR (p = 0.007) in postmenopausal women. The interaction models revealed significant interaction between WC, apoB and log HOMAIR (WC×apoB×log HOMAIR) on SBP (p = 0.001) adjusted for age. In a multivariate logistic regression, adjusting for age and apoB, WC (p = 0.001), log HOMAIR (p = 0.007) and menopause (p = 0.008) were significantly associated with higher risk for hypertension. These results suggest that changes in WC, apoB and IR accompanying menopause lead to a greater prevalence of hypertension in postmenopausal women.

Prevalence of diabetes in Northern African countries: the case of Tunisia.

BACKGROUND: Although diabetes is recognized as an emerging disease in African and Middle East, few population-based surveys have been conducted in this region. We performed a national survey to estimate the prevalence of type 2 diabetes (T2D) and to evaluate the relationship between this diagnosis, demographic and socioeconomic variables. METHODS: The study was conducted on a random sample of 6580 households (940 in each region). 7700 subjects adults 35-70 years old were included in the analyses. T2D was assessed on the basis of a questionnaire and fasting blood glucose level according to the WHO criteria. Access to health care and diabetes management were also assessed. RESULTS: Overall, the prevalence of T2D was 15.1%. There were sharp urban vs. rural contrasts, the prevalence of diabetes being twice higher in urban area. However, the ratio urban/rural varied from 3 in the less developed region to 1.6 in the most developed ones. A sharp increase of prevalence of T2D with economic level of the household was observed. For both genders those with a family history of T2D were much more at risk of T2D than those without. Awareness increase with age, economic level and were higher amongst those with family history of T2D. Drugs were supplied by primary health care centers for 57.7% with a difference according to gender, 48.9% for men vs. 66.0% women (p < 0.001) and area, 53.3% on urban area vs. 75.2% on rural one (p < 0.001). CONCLUSIONS: Through its capacity to provide the data on the burden of diabetes in the context of the epidemiological transition that North Africa is facing, this survey will not only be valuable source for health care planners in Tunisia, but will also serve as an important research for the study of diabetes in the region where data is scarce. In this context, NCDs emerge as an intersectoral challenge and their social determinants requiring social, food and environmental health policy.

Prevalence and determinants of the metabolic syndrome among Tunisian adults: results of the Transition and Health Impact in North Africa (TAHINA) project.

OBJECTIVE: To determine the prevalence of metabolic syndrome (MetS) and its components and to evaluate the relationship between this diagnosis and cardiovascular risk factors, demographic and socio-economic variables. DESIGN: A cross-sectional study using a questionnaire including information on sociodemographic and CVD risk factors. Blood pressure, anthropometric indices, fasting glucose and lipid profile were measured. MetS was defined according to the criteria of the National Cholesterol Education Program, Adult Treatment Panel III. SETTING: The whole Tunisian territory; Transition and Health Impact in North Africa (TAHINA) project. SUBJECTS: A total of 4654 individuals (1840 men and 2814 women), aged 35 to 74 years, who participated in the Tunisian national survey. RESULTS: The overall prevalence of MetS was 30·0 %, higher in women (36·1 %) than in men (20·6 %; P < 0·001). In both genders MetS prevalence increased significantly with age (P < 0·001), but this increase was more important in women. Multiple regression analyses showed that the odds for MetS increased significantly with urban area for both men and women (P < 0·05 and P < 0·001, respectively). The multivariate models showed also that the odds for MetS increased significantly with increasing level of education and in those with a family history of CVD for men (both P < 0·05) and after the menopausal transition for women (P < 0·05). CONCLUSIONS: The study highlights the MetS problem in a middle-income developing country. There is an urgent need for a comprehensive, integrated, population-based intervention programme to ameliorate the growing problem of MetS in Tunisians.

Relationship of plasma leptin and adiponectin concentrations with menopausal status in Tunisian women.

To evaluate the effect of menopausal status and body mass index (BMI) on circulating leptin and adiponectin concentrations and investigate whether there is an influence of menopausal transition on the relationships of these adipokines and leptin to adiponectin (L/A) ratio with lipid profile and insulin resistance in a sample of Tunisian women. One hundred ninety-six premenopausal (mean age 35.3±7.6 years) and 180 postmenopausal women (mean age 53.4±6.2 years) were included in the study. Participants were stratified into obese and normal weight groups based upon their baseline BMI. Fasting glucose, HDL-cholesterol (HDL-C), triglycerides (TG), total cholesterol (TC), insulin, leptin, and adiponectin concentrations were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Premenopausal women had significantly higher leptin and L/A ratio and lower adiponectin levels than postmenopausal women. Menopause had no effect on the mean values of BMI, insulin or HOMA-IR, HDL-C, and TG. Using a multiple linear regression model, menopausal status was identified, as significant independent predictor for leptin and adiponectin levels. Irrespective of the menopausal status, obese women exhibited higher leptin and L/A ratio and lower adiponectin levels compared to those with normal weight. Comparison between the two menopausal stages in obese and normal weight groups showed that leptin and L/A ratio decreased, while adiponectin increased from pre- to postmenopausal stage only in obese group. The L/A ratio correlated better with lipid profile and HOMA-IR in postmenopausal stage. The present study showed a significant interaction between menopause and BMI on leptin and adiponectin secretion. Menopausal transition affects the relationships of these adipokines with lipids and insulin resistance.

The Apolipoprotein B/Apolipoprotein A 1 ratio in relation to metabolic syndrome and its components in a sample of the Tunisian population.

OBJECTIVE: This study was undertaken to investigate the relationship between the Apolipoprotein B/Apolipoprotein A 1 (ApoB/ApoA 1) ratio and various characteristics of the metabolic syndrome (MetS) in a sample of the Tunisian population. METHODS: The study included 330 adults aged 35-74 (172 patients with MetS and 158 controls). Waist circumference (WC), blood pressure (BP), HDL-cholesterol (HDL-C), triglycerides (TG), glucose, insulin, and apolipoprotein concentrations were measured. Homeostasis model assessment (HOMA) was used to assess insulin resistance (IR). MetS was defined by NCEP-ATPIII report. RESULTS: The ApoB/ApoA 1 ratio was significantly higher in patients with MetS versus normal control subjects (p<0.001). Mean values of ApoB/ApoA 1 ratio increased significantly as the numbers of MetS components increased in men (p<0.001) and women (p<0.001). ApoB/ApoA 1 ratio showed statistically significant associations with WC, HDL-C, TG, systolic and diastolic BP, and HOMA-IR. After adjusting for age and gender, the high ApoB/ApoA 1 ratio was significantly associated with the presence of MetS (odds ratio [OR]=6.10), IR (OR=1.88), and with each of the MetS components, including: high WC (OR=2.43), High TG (OR=6.14), and low HDL-C (OR=6.92). CONCLUSIONS: Our findings suggest that the ApoB/ApoA 1 ratio is strongly associated with MetS and its components, as well as with IR.

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.

Menopause and metabolic syndrome in tunisian women.

OBJECTIVES: This study aimed to evaluate the effect of menopausal status on the risk of metabolic syndrome (MetS) in Tunisian women. METHODS: We analyzed a total of 2680 women aged between 35 and 70 years. Blood pressure, anthropometric indices, fasting glucose, and lipid profile were measured. The MetS was assessed by the modified NCEP-ATPIII definition. RESULTS: The mean values of waist circumference, blood pressure, plasma lipids, and fasting glucose were significantly higher in postmenopausal than in premenopausal women, a difference that was no longer present when adjusting for age. Except for hypertriglyceridaemia, the frequency of central obesity, hyperglycemia, high blood pressure, and high total cholesterol was significantly higher in postmenopausal than in premenopausal women. After adjusting for age, the significance persisted only for hyperglycemia. The overall prevalence of MetS was 35.9%, higher in postmenopausal (45.7% versus 25.6%) than in premenopausal women. A binary logistic regression analysis showed that menopause was independently associated with MetS (OR = 1.41, 95% CI 1.10-1.82) after adjusting for age, residence area, marital status, family history of cardiovascular disease, education level, and occupation. CONCLUSIONS: The present study provides evidence that the MetS is highly prevalent in this group of women. Menopause can be a predictor of MetS independent of age in Tunisian women.

Association between C-reactive protein and type 2 diabetes in a Tunisian population.

The aim of this study was to investigate the association of CRP levels with type 2 diabetes (T2D) and its related variables in a sample of the Tunisian population. Our sample included 129 patients with T2D and 187 control subjects. Body mass index (BMI), plasma lipids, glucose, insulin, and CRP concentrations were measured for each participant. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. T2D was defined as a fasting plasma glucose (FPG) level ≥ 7.0 mmol/L, the use of anti-diabetic drugs, or both. Statistical analyses were performed using SPSS 11.5. A significant difference in mean values of BMI, plasma lipids, FPG, insulin, and HOMA-IR was observed between subjects with and without T2D. CRP level was significantly higher in subjects with T2D than those without (p = 0.023), and this result persisted even after adjustment for age, gender, BMI, smoking, and alcohol consumption. In both diabetes statuses, log CRP was significantly associated with FPG, insulin, and HOMA-IR. Subjects with elevated CRP levels (>5 mg/L) had an increased risk of T2D (OR = 2.02, 95% CI 1.18-3.46, p = 0.010) than those whose CRP levels were less or equal to 5 mg/L. Even after adjustment for potentially confounding factors, the risk of T2D was still increased in subjects with elevated CRP levels (OR = 1.91, 95% CI 1.08-3.36, p = 0.025). These results suggest that elevated CRP levels are independently associated with T2D.

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.

Relationship of C-reactive protein with components of the metabolic syndrome in a Tunisian population.

BACKGROUND: C-reactive protein (CRP) is an independent risk factor of diabetes and cardiovascular disease and it is proposed as a component of metabolic syndrome (MS). This study was undertaken to investigate the relationship between CRP and various characteristics of the MS in a sample of the Tunisian population METHODS: One hundred and forty nine patients with MS and 152 controls, aged 35-70 years were recruited. Waist circumference (WC), blood pressure, HDL-cholesterol (HDL-C), triglycerides (TG), glucose, insulin and CRP were measured. Insulin resistance was assessed by homeostasis model assessment of insulin resistance (HOMA-IR). MS was defined by NCEP-ATPIII report RESULTS: CRP levels were significantly higher in MS group (4.41±3.73 mg/L vs. 2.68±2.59 mg/L, p<0.001) compared to without MS group. For both sexes, CRP increased as the number of MS components increased (p=0.015 for men and p<0.001) after adjustment for age, smoking, alcohol intake and, for women, menopause. There were statistically significant positive correlations for log CRP with WC, log TG, and log HOMA-IR in both sexes adjusted for confounding factors listed above. A significant negative correlation was found between HDL-C and log CRP only in women. In both sexes, WC was identified, by multiple linear regression models, as significant independent predictor of CRP level variability. HDL-C showed also a significant contribution only in women CONCLUSIONS: The present study provides evidence that CRP levels are elevated in MS subjects. In addition, WC and HDL-C are significant predictors of the CRP elevation.

Hypertension among Tunisian adults: results of the TAHINA project.

We performed a national survey to determine the prevalence, awareness, treatment and control of hypertension, one of the main cardiovascular risk factors, among the adult population in Tunisia. A total of 8007 adults aged 35-70 years were included in the study. Blood pressure (BP) measurements were taken by physicians with a mercury sphygmomanometer, and standard interviewing procedures were used to record medical history, socio-demographic and cardiovascular disease (CVD) risk factors. Hypertension was defined as a systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg or current treatment with antihypertensive drugs. The prevalence of hypertension was 30.6%, higher in women (33.5%) than in men (27.3%). Multiple logistic regression analyses identified a higher age, urban area, higher body mass index, type 2 diabetes and family history of CVD as important correlates to the prevalence of hypertension. Only 38.8% of those with hypertension were aware of their diagnosis, of which 84.8% were receiving treatment. BP control was achieved in only 24.1% of treated hypertensive persons. Women were more aware than men (44.8 vs. 28.8%), but the rates of treatment and control of hypertension did not differ between the two genders. Higher age, being female, lower education level and urban area emerged as important correlates of hypertension awareness. The study highlights the hypertension problem in a middle-income developing country. There is an urgent need for a comprehensive integrated population-based intervention program to ameliorate the growing problem of hypertension in Tunisians.

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.

Association of G-2548A LEP polymorphism with plasma leptin levels in Tunisian obese patients.

OBJECTIVES: The aim of this study was to examine the association of the G-2548A polymorphism of the human leptin gene (LEP) with body mass index (BMI), plasma leptin, insulin, and lipid parameters in a sample of Tunisian population. DESIGN AND METHODS: Two hundred and twenty nine obese patients (BMI>or=30 kg/m(2)) were screened and compared to 251 normal weight subjects (BMI<25 kg/m(2)). The human leptin gene promoter G-2548A genotype was determined by polymerase chain reaction followed by a digestion with the restriction of endonuclease CfoI. RESULTS: In the entire study sample, carriers of -2548A allele had significantly lower leptin levels than homozygous for -2548G allele (14.28+/-9.10 ng/mL vs. 18.27+/-12 ng/mL, p<0.001 respectively) adjusted for BMI and gender. In obese patients but not control, subjects carrying the -2548A allele exhibited lower leptin levels than those with GG genotype (16.96+/-8.27 ng/mL vs. 21.37+/-11.72 ng/mL, p=0.001 respectively) adjusted for BMI and gender. In this group, carriership of the -2548A allele was identified, by multiple linear regression models, as significant independent predictor for leptin levels variability. Separate analyses by gender revealed that only in obese women, the -2548A allele was found to be associated with lower leptin levels independently of BMI (p=0.004). CONCLUSIONS: The present study showed that G-2548A LEP polymorphism is associated with lower leptin levels in Tunisian obese women.

LEPR p.Q223R Polymorphism influences plasma leptin levels and body mass index in Tunisian obese patients.

BACKGROUND AND AIMS: The leptin receptor (LEPR) plays a crucial role in the regulation of body weight. Several common polymorphisms have been described in the human LEPR gene including the p.Q223R polymorphism (rs1137101). The association of this polymorphism with obesity or related metabolic phenotypes has been controversial. The aim of this study was to investigate the impact of the LEPR p.Q223R polymorphism on body mass index (BMI), plasma leptin and lipid parameters in a sample of the Tunisian population. METHODS: The study included 391 obese patients and 302 normal weight subjects. LEPR p.Q223R genotypes were identified by the PCR-RFLP analysis. RESULTS: Obese patients homozygous for RR genotype showed lower leptin levels than those with other genotypes (p = 0.005) adjusted for age, BMI and gender. Stratified analysis by gender revealed that obese male patients carrying the R allele showed significantly lower BMI (p = 0.007) and leptin levels (p = 0.037) than subjects homozygous for the Q allele. In obese women, the LEPR p.Q223R polymorphism was found associated with lower leptin concentrations (p = 0.05). After adjustment for age and BMI, the association between the LEPR variant and plasma leptin remained significant only within female patients (p = 0.027). A general linear model including leptin as dependant variable and age, BMI, menopausal status and genotype as covariates revealed that the LEPR p.Q223R polymorphism is independently associated with leptin levels in obese women (p = 0.026). CONCLUSIONS: Our findings suggest that the LEPR p.Q223R polymorphism influences plasma leptin levels and BMI in obese patients.

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 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.

Gender-specific effect of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma-2 gene on obesity risk and leptin levels in a Tunisian population.

OBJECTIVES: This study was undertaken to investigate the impact of the Pro12Ala (rs1801282) polymorphism of the peroxisome proliferator-activated receptor gamma-2 (PPARgamma-2) gene on obesity or body mass index (BMI) and plasma leptin, insulin, adiponectin and lipid levels in a sample of the Tunisian population. DESIGN AND METHODS: The study included 387 obese patients and 288 control subjects. The Pro12Ala genotype was determined by polymerase chain reaction followed by a digestion with the restriction of endonuclease BstUI. RESULTS: In the whole population, there is no significant difference in genotype frequencies of the Pro12Ala polymorphism between obese patients and controls. However, separate analysis by gender revealed that obese men (but not women) had significantly higher frequency of Pro/Ala genotypes compared to controls (12.2% vs. 4.1%; chi(2)=6.76, p=0.009). In comparison to Pro/Pro homozygotes, Ala-allele bearers had a significantly higher risk of obesity [OR (95% CI)=3.26 (1.28-8.33)]. When obese subjects were stratified according to type 2 diabetes status, the association with obesity was only significant in obese non-diabetic patients [OR (95% CI)=3.74 (1.43-9.74), p=0.007]. Additionally, obese male patients carrying the Ala-allele had significantly higher body mass index (p=0.007) and plasma leptin levels (p=0.023) compared to those homozygous for Pro-allele. The significant effect of Pro12Ala polymorphism on plasma leptin levels disappeared after adjustment for age and BMI. CONCLUSION: The present study provides evidence that the Pro12Ala polymorphism of the PPARgamma-2 gene is associated with obesity in non-diabetic men from Tunisian origin.

Association between the 2756A> G variant in the gene encoding methionine synthase and myocardial infarction in Tunisian patients.

BACKGROUND: Elevated plasma total homocysteine (tHcy), a risk factor for coronary artery disease (CAD), is due to defects in genes encoding for enzymes involved in tHcy metabolism or from inadequate status of vitamins involved in tHcy disposal. Methionine synthase (MS), a vitamin B(12)-dependent enzyme, catalyses the remethylation of homocysteine to methionine using a methyl group donated by 5-methyltetra-hydrofolate, which is the major circulating form of folate in the body. Functional genetic variants of the MS may alter tHcy as well as folate levels which are independent risk factors for CAD. The influence of a common genetic polymorphism 2756A>G of the MS gene (MTR) on plasma tHcy, folate and vitamin B(12) levels and its relation to the risk of myocardial infarction (MI) in a Tunisian case-control study was investigated. METHODS: A total of 321 Tunisian patients with MI and 343 healthy controls were included in the study. The 2756A>G variant of the MTR was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Plasma tHcy was assessed with a fluorescent polarising immunoassay method. Plasma vitamin B(12) and folate were determined by microparticular enzyme immunoassay and ion-capture, respectively. RESULTS: A significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with MI had a frequency of 1.9% for the GG genotype, 26.2% for the AG genotype and 72% for the AA genotype. Controls had a frequency of only 0.9% for the GG genotype, 18.7% for the AG genotype and 80.5% for the AA genotype (chi(2)=6.97, p=0.03). The MI patient group showed a significant higher frequency of the G allele compared to controls (0.149 vs. 0.101; OR 1.55; 95% CI 1.10-2.18; p=0.008). The association between the 2756A>G variant in the gene encoding MS and MI was no longer significant after adjustment for other well-established risk factors. When clinical and laboratory values were compared amongst genotypes in the study groups, no significant differences were noted. CONCLUSIONS: The present study showed a significant but not independent association between the 2756A>G polymorphism of the MTR (presence of G allele) and MI in the Tunisian population.

Association of the insertion/deletion gene polymorphism of the apolipoprotein B signal peptide with myocardial infarction in Tunisian patients.

BACKGROUND: Numerous polymorphisms of the apolipoprotein B (APOB) gene have been described. Particularly, the insertion/deletion (Ins/Del) polymorphism located in the coding part of the signal peptide of apoB, associated with modification of lipid concentrations and the risk of coronary artery disease and/or myocardial infarction (MI), has been reported in the general population. Moreover, conflicting results emerge from the literature and suggest that the effect is context-dependent. In the present study, the first investigation of the Ins/Del polymorphism of the APOB gene in Tunisian patients with MI, we examined a possible association between this polymorphism and MI in a subgroup of the Tunisian population. METHODS: A total of 318 Tunisian patients with MI and 368 healthy controls were included in the study. Genomic DNA was extracted from white blood cells, and the Ins/Del polymorphism was determined by electrophoresis in polyacrylamide gels after PCR amplification. A binary logistic regression analysis was performed to test how the association between MI and Ins/Del polymorphism is independent from confounding factors. RESULTS: A significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with MI had a frequency of 7.2% for the Del/Del genotype, 39.6% for the Ins/Del genotype, and 53.1% for the Ins/Ins genotype. Controls had a frequency of 3.0% for the Del/Del, 32.1% for the Ins/Del and 64.9% for the Ins/Ins genotype (chi2=12.93, p=0.002). The MI patient group showed a significantly higher frequency of the Del allele compared to controls (27.1% vs. 19.1%; chi2=12.50, p=0.0004). In comparison to the Ins/Ins homozygotes, the odds ratio (95% confidence interval) for MI was 1.51 (1.09-2.07) for Ins/Del heterozygotes and 2.95 (1.40-6.22) for Del/Del homozygotes. In multivariate analysis, age (p=0.001), smoking (p<0.001), hypertension (p=0.001), diabetes mellitus (p<0.001), and dyslipidemia (p=0.01) were independent correlates of the presence of MI, whereas the Ins/Del polymorphism (p=0.330) was not an independent predictor of MI. CONCLUSIONS: The present study shows a significant but not independent association between the Ins/Del polymorphism of the APOB gene and MI in the Tunisian population.

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

BACKGROUND: 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 myocardial infarction (MI) have been reported. In the present study, we examined a possible association between a 27-base pair (bp) repeat polymorphism in intron 4 of the NOS3 gene and MI in a subgroup of the Tunisian population. METHODS: A total of 310 Tunisian patients with MI and 250 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 difference in genotype distribution and allele frequency was observed between patients and controls. Patients with MI had a frequency of 4.8% for the 4a4a genotype, 33.9% for the 4a4b genotype and 61.3% for the 4b4b genotype. Controls had a frequency of only 1.6% for the 4a4a genotype, 24.4% for the 4a4b genotype and 74.0% for the 4b4b genotype (chi2=11.81, p=0.003). The MI patient group showed a significant higher frequency of the 4a allele compared to controls (0.218 vs. 0.139; chi2=5.81, p=0.01). CONCLUSIONS: In the present study, a significant association between the NOS34a/4b gene polymorphism (presence of 4a allele) and MI in the Tunisian population was found.