Association of ADIPOQ, leptin, LEPR, and resistin polymorphisms with obesity parameters in Hammam Sousse Sahloul Heart Study.

BACKGROUND: Adipose tissue is an important endocrine organ that secretes a number of adipokines, such as adiponectin (ADIPOQ), leptin (LEP), leptin receptor (LEPR), and resistin (RETN) which may be implicated in obesity. Some adipokines' polymorphisms of genes might influence their concentrations and/or activities. Our aim was to study the relationship between seven SNPs in ADIPOQ (+45T

Association between haptoglobin 2-2 genotype and coronary artery disease and its severity in a tunisian population.

Haptoglobin (Hp) polymorphism generates three common human genotypes (Hp1-1, Hp2-1, and Hp2-2), having functional differences, related to the risk of development of cardiovascular diseases. These functions are a consequence of hemoglobin binding that leads to the synthesis of an antioxidant like ferritin. We explored the association of Hp polymorphism with significant coronary stenosis (SCS) and its severity within 400 Tunisian patients, using genotyping, biochemical parameters, and the Gensini score. After adjustments for age and gender, Hp2-2 was associated with the highest ferritin but the lowest Hp concentrations. After adjustments for confounding parameters, the OR of SCS associated with Hp2-2 was 1.74 (95% CI 1.18-2.58; p = 0.005). This effect was enhanced within diabetics (OR 1.90, 95% CI 1.11-3.24; p = 0.018), obese subjects (OR 1.98, 95% CI 1.10-4.86; p = 0.034), and smokers (OR 4.17, 95% CI 1.54-1.29; p = 0.005). The Hp2-2 genotype is associated with an increase in SCS especially in diabetics, the obese, and smokers.

DPYD and TYMS polymorphisms as predictors of 5 fluorouracil toxicity in colorectal cancer patients.

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer death. 5-Fluorouracil (5-FU) is an essential component of systemic chemotherapy for CRC. Our objective was to determine the genotypic frequency of polymorphisms affecting dihydropyrimidine dehydrogenase (DPYD) and thymidylate synthetase (TYMS) genes and to correlate the genetic profile with the toxicity due to 5-FU, also considering nongenetic factors. This is a prospective study that involved 66 patients. We extracted DNA by salting out methods. We carried out the genotyping of the different polymorphisms by simple PCR for the TYMS 5'UTR and by PCR-RFLP for DPYD: 1905 + 1 G > A, 85 T > C, 496 A > G, 1679 T > G, c.483 + 18G > A and the TYMS: 5'UTR VNTR, 5'UTR G > C and 3'UTR. The study of the association of DPYD and TYMS polymorphisms with the various signs of toxicity under 5-FU revealed that the polymorphisms 496 A > G were significantly associated with hepatotoxicity: OR = 3.85 (p = 0.04). In addition, 85 T > C was significantly associated with mucositis and neurotoxicity: OR = 4.35 (p = 0.03), OR = 3.79 (p = 0.02). For TYMS, the only significant association we observed for 5'UTR with vomiting: OR = 3.34 (p = 0.04). The incidence of adverse reactions related to 5-FU appears to be influenced in patients with CRC by the identified DPYD and TYMS gene polymorphisms in the Tunisian population.

Six lipoprotein lipase gene polymorphisms, lipid profile and coronary stenosis in a Tunisian population.

Lipoprotein lipase (LPL) is the rate-limiting enzyme in the hydrolysis of triglyceride-rich lipoprotein particles (Chylomicrons and very-low-density lipoprotein). LPL polymorphisms' effects on lipids and coronary artery disease are controversial among studies and populations. Our aim was to study the association between six polymorphisms, haplotypes and significant coronary stenosis (SCS), disease severity and lipid parameters in Tunisian patients. LPL PvuII, 93 T/G, 188 G/E, HindIII, N291S and D9N polymorphisms were analyzed in 316 patients who underwent coronary angiography. Assessment of coronary angiograms identified SCS as the presence of stenosis >50 % in at least one major coronary artery. The stenosis severity was determined by using Gensini score and vessels number. A significant association of SCS with TT of the HindIII polymorphism was showed (odds ratio (OR): 2.84, 95 % CI, 1.19-7.40, p = 0.017) and TG (OR: 1.77, 95 % CI, 1.99-2.82, p = 0.033). The mutated HindIII genotype was significantly associated with increased TG and ApoB/ApoA-I ratio and with decreased HDL-C. Haplotype analysis showed that OR of SCS associated with the CTGTAG haplotype was 2.12 (95 % CI 1.05-4.25, p = 0.032) and with CGGGAA was 0.71 (95 % CI 0.26-1.95, p = 0.022) compared to the CTGTAA. Significant difference in Gensini score was observed among HindIII genotype and haplotypes. A significant association between the mutated genotype of HindIII polymorphism and decreased HDL-C level and increased ApoB/ApoA-I ratio and TG level was showed. Our results suggest that HindIII and D9N polymorphisms and CTGTAG haplotype seem to be considered as marker of predisposition to coronary stenosis. In another hand, HindIII and haplotypes were related to stenosis severity.

Epidemiology of arterial hypertension in Tunisia: Hammam Sousse Sahloul Heart Study (HSHS).

INTRODUCTION: Tunisia is experiencing a double burden of morbidity, characterized by the explosion of cardiovascular diseases and their risk factors including arterial Hypertension. The objective of this study, based on the HSHS cohort (Hammam Sousse Sahloul Heart Study), was to determine the prevalence of hypertension in the general population and to identify its predisposing factors. METHODS: HSHS is a cardiovascular health promotion initiative in the city of Hammam Sousse (Tunisia). The study was conducted via a random sample of households, using the WHO PEV technique, made up of 33 clusters, of 33 households each. All people aged 20 and over, included, benefited from a questionnaire, a physical examination and a biological assessment. The Systolic Blood Pressure (SBP) and the Diastolic Blood Pressure (DBP) were measured from the average of the last two measurements, by an OMRON type tensiometer, of suitable width. These prevalences were adjusted according to sex and age group, by their weighting coefficients in the general population, and they were accompanied by their 95% CIs. Binary logistic regression was conducted to identify independent factors associated with hypertension. RESULTS: The study population was composed of 481 men (33.4%) and 960 women (66.6%), with an average age of 49.6±16.35 years in males (M) and 46.6±16.18 in females (F). In addition to the family history of hypertension, the sufficient weekly consumption of vegetables and fruits was low (M: 32.4%, F: 24.9%). The adjusted rate of hypertension in the adult study population was 32.5%, 95%CI[31.9-33.1] (M: 36.4%, 95%CI[35, 5-37.3]; F: 28.4%; 95% CI[27.6-29.2]), reaching in the age group of 60 years and above: M: 74.6% (95%CI[66.9-82.3], F: 82.7% (95%CI[73.8-83.6]) Multivariate analysis identified five independent factors significantly associated with hypertension: male sex (ORa=1.55 [1.18-2.03]), age over 40 years (ORa=6.54[4.70-9.11]), low level of schooling (ORa=1.80 [1.36-2.38]), low physical activity (ORa=1.42[1.07-1.88]) and high socio-economic level (ORa=1 .84 [1.30-2.63]). CONCLUSION: The HSHS study confirmed the high prevalence of hypertension, and the extent of its low detection and control. Hence the need for a universal approach to health promotion, oriented towards the general population, piloted by its local organizations, based on the adoption of a healthy lifestyle, and centered on physical activity.

Epidemiology of obesity in Tunisia: HSHS4 study (Hammam Sousse Sahloul Heart Study).

INTRODUCTION: The HSHS study is a community-based survey focused on cardiovascular risk factors. AIM: The objectives of this specific analysis were to determine the prevalence of obesity and overweight in the general population of Hammam Sousse (Tunisia) and to identify their predisposing factors. METHODS: HSHS was conducted with a random sample of households, composed by the EPI (Expanded Program on Immunization) technique. All people aged 20 and over, met on the day of the survey, at their homes, were included. Obesity, overweight and weight overload were defined with reference to Body Mass Index (BMI): Obesity (BMI≥30 kg/m²), Overweight (25≤BMI (25≤BMI <30 kg/m²), weight overload (BMI≥25 kg/m²). Physical activity was evaluated according to the level of energy equivalents (Metabolic Equivalent Task) or MET, this level was considered low below 600 MET min/week. The calculated prevalences were accompanied by their 95%CI (Confidence Intervals). The multivariate study was conducted by logistic regression, measuring the adjusted Odds Ratio (ORa) Results: The study population was composed of 481 men and 960 women, (sex-ratio=0.50). The age ranged from 20 to 96 years with an average of 49.6±16444 years in men and 46.6±16.2 in women (p <0.05). After adjusting for age and sex, the prevalence rates of overweight, obesity, and weight overload were respectively 36.18%, 95%CI [35.38%-36.62%], 28.11%; 95%CI [27.42%-28.58%] and 64.28%; 95%CI [63.38%-64.62%]. Obesity was determined, in addition to female sex, age 40 or over and low level of education, by low level of physical activity (ORa=1.56; 95%CI [1.21-2.03], p<10-2). CONCLUSION: In adults, the prevalence of obesity and overweight were high and determined by insufficient physical activity. The results of this study, which can be extrapolated to other Tunisian cities, should motivate the general population to establish a heart health promotion plan, in partnership with civil society.

Epidemiology of diabetes mellitus in Tunisia. HSHS 2 study (Hammam Sousse Sahloul Heart Study).

BACKGROUND: National epidemiological studies on diabetes mellitus are rare, ancient and often carried out schools or clinics settings. OBJECTIVES: To determine the prevalence of diabetes mellitus and identify its risk factors in the adult population of the city of Hammam Sousse (Tunisia) during the year 2009. METHODS: This study is a part of analysis of the HSHS database (Hammam Sousse Sahloul Heart Study), a «community-based¼ cross-sectional study on cardiovascular risk factors including diabetes mellitus, with a two-stage proportional probability cluster random sample. All subjects aged 20 years and more underwent a lifestyle interview, clinical examination with anthropometric measurements, and blood sampling. The diagnosis of diabetes mellitus was defined by a fasting blood glucose level ≥7 mmol/l. Overweight was defined by a Body Mass Index (BMI) ≥ 25 kg/m². A multivariate logistic regression analysis was conducted to determine independent risk factors associated with diabetes mellitus. RESULTS: The population was composed of 481 males (M) and 960 females (F), a sex ratio of 0.5 with mean ages respectively of 49.6±16.35 years and 46.6±16.18 years. The prevalence of diabetes mellitus adjusted by age and sex was 12.1% (95%CI[11.7-12.5]); M: 12.7% (95%CI[12.1-13.3]), F: 11.5% (95%CI[10.9-12.1]). The prevalence rate of patients newly detected with diabetes mellitus was 1.9% (95%CI[1.7-2.1]): M: 1.8% (95%CI[1.6-2.0]), F: 2.1% (95%CI[1.8-2.4]). The multivariate study revealed five independent factors significantly associated with diabetes mellitus. In addition to non-modifiable factors (male gender, age ≥40 years old, low schooling level and family history of diabetes), diabetes mellitus was 2 (95%CI[1.3-3.2]) times more prevalent in overweight cases. CONCLUSION: In deep trouble of this epidemiological situation of diabetes mellitus, it is urgent to launch a universal intervention strategy based on the promotion of a healthy lifestyle motivating regular physical activity and a low-calorie diet.

Epidemiology of dyslipidemia in Tunisia, HSHS 3 study (Hammam Sousse Sahloul Heart Study).

INTRODUCTION: Dyslipidemia is a major cause of morbidity and mortality worldwide because it increases the risk of cardiovascular diseases. AIM: To determine the prevalence of dyslipidemia and its components in the general population of Hammam Sousse (Tunisia) and to identify its risk factors. METHODS: This was an analysis of the HSHS database (Hammam Sousse Sahloul Heart Study), a «community-based¼ cross-sectional study on cardiovascular risk factors including dyslipidemia, with a random sample in two-stages, proportional-probability clusters. All subjects above 20 years underwent a lifestyle interview, clinical examination with anthropometric measurements, and blood sampling. Dyslipidemia was defined by: total cholesterol ≥5.2 mmol/l, hyper LDL (Low Density Lipoprotein) cholesterolemia ≥4.1 mmol/l, hypo HDL (High Density Lipoprotein) cholesterolemia <1.03 mmol/l for men and <1.29 mmol/l for women and hyper-triglyceridaemia: ≥2.26 mmol/l. Multivariate logistic regression analysis was conducted to determine factors independently associated with dyslipidemia. RESULTS: The study population was composed of 481 males (M) and 960 females (F), with a sex ratio of 0.5. Mean cholesterol was higher in women (5 mmol/l±1.01) than in men (4.8 mmol/l±0.92). Only 24.9% of men and 29.1% of women had normal HDL cholesterol levels. Women had higher levels of hypercholesterolemia and LDL cholesterolemia than men (p<10-6). Multivariate analysis showed that dyslipidemia was independently and statistically significantly associated with age ≥40 years (p<10-3), physical inactivity (p<10-3) and obesity (p=0.025). CONCLUSION: As a result of the epidemiological situation of dyslipidemia, the promotion of an active lifestyle seems essential. In addition, nutritional education improves the lipid profile by promoting weight loss and balancing lipid consumption.

Epidemiology of metabolic syndrome in Tunisia. HSHS 5 study.

OBJECTIVE: To measure the prevalence of metabolic syndrome and its components in the HSHS cohort (Hammam Sousse, Tunisia), in 2009, and to identify its determining factors. METHODS: This was a descriptive epidemiological study of the "community based" type having focused on a random sample of people aged 20 and over. The metabolic syndrome was defined according to the criteria of the "International Diabetes Federation" (IDF 2005) and those of the "National Cholesterol Education Program-Adult Treatment Panel III" (NCEP-ATP III, 2001). RESULTS: The study involved 1441 people including 960 women (66.6%). The age- and sex-adjusted prevalences of increased waist circumference, blood pressure, blood sugar and triglycerides, and decreased HDL-cholesterol were respectively 63.2%, 95%CI[62.5-63.8]; 47.7%, 95%CI[47.4-48.6]; 25.7%, 95%CI[25.1-26.2]; 11.9%, 95%CI[11.4-12.3] and 65,6%, 95%CI[65.0-66.2], according to IDF thresholds and 37.4%, 95%CI[36.3-37.6]; 45.7%, 95%CI[45.4-46.6]; 13.8%, 95%CI[13.4-14.2]; 8.4%, 95%CI[8.0-8.7] and 61.9%, 95%CI[61.2-62.5], according to those of the NCEP-ATP III. The prevalence of metabolic syndrome adjusted for age and sex was 36.5% 95%CI[33.0%-38.9%] according to the IDF definition and 23.0% 95%CI[20.4%-25.6%] according to that of NCEP-ATP III. The multivariate study by logistic regression made it possible to retain three significant independent determining factors of the metabolic syndrome: age ≥40 years, low level of physical activity and family history of diabetes mellitus with respectively adjusted ORs of 3.77 95%CI[2.70-5.27], 1.39 95%CI[1.01-1.89], 1.62 95%CI[1.21-2.15], according to IDF and 5.87 95%CI[3.88 -8.88], 1.47 95%CI[1.07-2.01] and 1.45 95%CI[1.07-1.96], according to NCEP-ATP III . CONCLUSION: With this high prevalence rate of the metabolic syndrome, the establishment of an action plan would be essential. This plan should be based on the combination of the promotion of physical activity and screening for the components of the metabolic syndrome, particularly in subjects aged 40 or over, with a family history of diabetes mellitus.

[Epidemiology of smoking in the male population in Tunisia. HSHS Study 6].

OBJECTIVES: To determine the prevalence of smoking in the male population of Hammam Sousse (Tunisia), to describe its modalities and to analyse its determining factors. METHODS: This was a "community-based" study, carried out on a random sample of households, including a population of males aged 20 or over. The data were collected, at home, using a specific support consisting of a lifestyle questionnaire, a physical examination, and a biological assessment, oriented towards cardiovascular risk factors. Smoking behaviour covered both forms of cigarettes and Narghile. "Current smokers" included all men declaring that they smoked at the time of the survey, including "regular smokers", who smoked daily at the time of the survey, and "occasional smokers", less than once a day. The group of "non-smokers" at the time of the survey was the sum of "ex-smokers" and those "who had never smoked". The prevalences were calculated after their weighting according to age and the adjusted odds ratios were measured following a multivariate study by logistic regression. RESULTS: The study population was composed of 481 men with an average age of 49.6±16.35 years and a median of 49 years. Mean body mass index and systolic blood pressure were 26.9 kg/m2 ±4.20 and 151.9 mmHg±24.36, respectively. After adjusting for age, the proportions of current users, former users and subjects who had never used tobacco (all forms combined) were respectively 50.4% (95% CI [49.49-51.3]), 17.4% (95% CI [16.71-18.08]) and 30.9% (95% CI [30.06-31.73]). Daily cigarette consumption was characterized by an average onset at age 20.1±6.91 years, an average duration of 27.0±15.22 years and an average amount of 17.6±9.8 cigarettes smoked per day. After adjusting for age, level of education, and socioeconomic level, smoking behaviour was attributed to a single independent risk factor: the presence of a smoker in the family, with an adjusted OR of 45.17 (p (p<10-3) for regular cigarette smokers, and 29.66 for regular tobacco users of all forms. CONCLUSION: Smoking would be a real endemic in Tunisia, threatening the cardiovascular health of the country. The national health system is called upon to strengthen its action plan for the prevention and control of smoking, in all living environments: family, school, work, health centre, etc.

Epidemiology of elderly dependency in Tunisia. HSHS study 7.

AIM: Measure the functional autonomy of elderly people and identify its components and determinants in the HSHS (Hammam-Sousse Sahloul Heart Study) population (phase 2009, Tunisia). METHODS: This study was concerned with the quality of life of elderly people aged 65 years or more, living at home from the HSHS cohort divided into two groups: young-old (65-74 years old) and old-old (≥75 years old). The autonomy was assessed using the "Activities of Daily Living" (ADL) scale ranging from 0 to 6, the "Instrumental Activities of Daily Living" (IADL) scale ranging from 0 to 8 and, the combined scale ranging from zero to 14, iso-weighted at one point per activity. Autonomy in daily activities was retained for an ADL score=6, and an IADL score (F=8; H=5). Subjects with an overall score (sum of ADL and IADL) of 10-14 points were considered globally autonomous. RESULTS: The population study was predominantly female (sex-ratio=0,6) with an important proportion of old-old (M=43%, F=37%). Autonomy rates were by ADL (M=57.4%, F=36.1%, p < 10-2), IADL (M=16%, F=23.9%), and by combined score (M=60.6%, F=69%, p=NS). The typology of dependency was dominated by transferring (M=35%, F=61%) and bathing (M=14%, F=19%) for ADL activities, and shopping (M=36%, F=49%) and the use of means of transport (M=22%, F=43%) for IADL activities. After adjustment, autonomy in daily activities was attributed to two independent factors: male sex (ORa=3.98, CI95% [1.328-11.971]) and age group 65-75 (ORa=4.04, CI95% [2.039- 8.025]). Autonomy in instrumental activities was associated with age group (ORa=31.5, CI95% [4.087-233.514]). Finally, overall autonomy (current and instrumental) was associated independently after logistic regression, with four independent factors, two of which were not modifiable: being female (ORa=3.1, CI95% [1.2-8.1]) and 65 to 75 years (ORa=6.2, CI95% [3.1-12.3]) and two modifiable factors: no recent hospitalization (ORa=3.8, CI95% [1.4-10.4]) and a sufficient level of physical activity (ORa=2.6, CI95% [1.3-5.3]). CONCLUSION: The physical dependency rate of the elderly is very high in Tunisia. The promotion of physical activity, the extension of similar studies and the development of could improve the support of these people.

Association between four resistin polymorphisms, obesity, and metabolic syndrome parameters in Tunisian volunteers.

Resistin is an adipocyte-secreted cytokine recently discovered and has been proposed as a link between obesity and diabetes. Many resistin gene polymorphisms were described and their implication in obesity and metabolic syndrome (MetS) was controversial. Our aim was to study the relationship between four resistin polymorphisms (420C/G, 44G/A, 62G/A, and 394C/G), MetS parameters, and the risk of obesity in Tunisian volunteers. We recruited 169 nonobese (sex ratio=0.594; mean age=43.25±13.12 years; mean body mass index [BMI]=24.73±3.50 kg/m(2)) and 160 obese subjects (sex ratio=0.221; mean age=48.41±10.92 years; mean BMI=36.6±4.8 kg/m(2)). Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism. Anthropometric parameters, lipid levels, glycemia, and insulinemia were measured. BMI was calculated and insulin resistance was evaluated with the homeostasis model assessment insulin resistance (HOMA-IR). Statistical analyses were performed by SPSS 17.0. The 420C/G seems to contribute to obesity. In fact adjusted odds ratio (OR) of obesity associated to mutated genotypes was 2.17 and 95% confidence interval was 1.28-3.68 (p=0.004). Mutated genotypes at 420C/G were associated with higher waist circumference and BMI. In addition, 44G/A polymorphism was associated with increased total cholesterol and low-density lipoprotein-cholesterol levels. The other genotypes showed no association with MetS parameters. Concerning association between single-nucleotide polymorphisms and MetS risk, only mutated genotypes at 44G/A increase the risk of MetS after adjustment to confounding parameters (OR=1.93, p=0.023). In conclusion, resistin gene polymorphisms 420C/G and 44G/A were associated with obesity and MetS parameters in Tunisian volunteers.

Relationship between leptin G2548A and leptin receptor Q223R gene polymorphisms and obesity and metabolic syndrome risk in Tunisian volunteers.

Leptin is a key hormone of weight regulation that modulates food intake. Since the elaboration of the leptin action mechanism, several studies tried to establish the relationship between obesity and the common polymorphisms of leptin (LEP) and leptin receptor (LEPR) genes, but results were controversial. We studied the association of G2548A of the LEP gene and Q223R of LEPR gene polymorphisms with obesity and metabolic syndrome (MetS). We recruited 169 nonobese volunteers (body mass index [BMI] < 30 kg/m(2)) and 160 obese ones (BMI ≥ 30 kg/m(2)). Glucose, insulin, and lipids were measured. BMI, homeostasis model assessment-insulin resistance (HOMA-IR), and daily energy intake were calculated. After adjustment to confounders parameters, 2548AA was found to increase the MetS (p=0.043) and obesity risk (p=0.019) in the studied population. After stratification according to the degree of obesity, the odds ratio [OR] of 2548AA was associated with moderate obesity (p=0.048) and morbid obesity (p=0.048). The LEPR 223RR genotype was associated with obesity in the studied population (OR=1.74, p=0.037) and only in the overweight (OR=1.8, p=0.049). Subjects with 2548AA had significantly higher BMI, daily energy intake, total cholesterol (TC), waist circumference (WC), insulinemia, and low high-density lipoprotein-cholesterol (HDL-C) levels. With regard to 223RR, we noted a significantly higher daily energy intake, BMI, TC, glycemia, insulinemia, HOMA-IR index, and low HDL-C levels. Haplotype model AR (2548A+223R) and AQ (2548A+223Q) increased the risk of obesity (OR=3.36, p<0.001; OR=2.56, p=0.010, respectively). When we added daily energy intake in adjustment, these significant associations disappeared. In addition, the AR and AQ increased the MetS risk. This significant association persisted after we had added daily energy intake in adjustment. This study showed that LEP G2548A and LEPR Q223R polymorphisms and haplotype combination were associated with MetS and obesity risk in Tunisian volunteers.

Single-nucleotide polymorphisms at the adiponectin locus and risk of coronary artery disease in Tunisian coronaries.

OBJECTIVE: Adiponectin is an adipocyte-derived hormone and an essential modulator of insulin sensitivity. Several studies suggest an important role of adiponectin in the process leading to atherosclerosis, thus indicating the adiponectin gene as a potential candidate for coronary artery disease. Two single-nucleotide polymorphisms (SNPs) at the adiponectin locus (+45T/G and +276G/T) have been associated with low circulating adiponectin levels, insulin resistance and type 2 diabetes. The objective was to examine the association of two SNPs (45T/G and 276G/T) with coronary artery disease in a Tunisian population. METHODS: We have recruited 316 Tunisian patients, documented by coronary angiography. Significant coronary stenosis (SCS) was defined as a luminal narrowing of at least 50% in at least one major coronary artery. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism. Lipids and apolipoproteins were measured. RESULTS: After adjustments for confounder parameters, odds ratio (OR) of SCS associated with 276G/T mutated genotypes was 0.472 [95% confidence interval (CI) 0.195-0.842, P=0.046]. The mutated genotypes at the +45T/G polymorphism were significantly associated with increased SCS only in obese patients (OR 3.31, 95% CI 0.996-11.05, P=0.049 versus OR 1.71, 95% CI 0.467-6.269, P=0.418 in non-obese individuals). A potential protective effect was also observed for the haplogenotype TT/TT (OR 0.548, 0.306-0.982, P=0.043) in all the studied population. CONCLUSION: Mutated genotypes at +45T/G (GG + TG) were associated with an increase in SCS only in the obese group. Mutated genotypes at +276G/T (TT + GT) seem to reduce the risk of SCS in the studied population. When the two SNPs were combined, the TT/TT haplogenotype (normal genotype at 45T/G and mutated genotype at 276G/T) was associated with a protective effect.

Apolipoprotein B and non-high-density lipoprotein cholesterol are better risk markers for coronary artery disease than low-density lipoprotein cholesterol in hypertriglyceridemic metabolic syndrome patients.

BACKGROUND: Metabolic syndrome is highly prevalent in the general population. Small dense low-density lipoprotein (sd-LDL) particles have been considered as a risk marker in metabolic syndrome diagnosis. Apolipoprotein B (ApoB) concentration reflects the number of LDL particles and is closely associated with atherosclerosis. The aim of this study was to compare the associations of ApoB, non-high-density lipoprotein cholesterol (NHDL-C), and low-density lipoprotein cholesterol (LDL-C) with metabolic syndrome and its relationship with significant coronary stenosis (SCS) in a Tunisian population. METHODS: We enrolled 192 patients, who underwent coronary angiography. The body mass index, blood lipids, fasting glucose, insulin concentration, and blood pressure of every patient were measured. Metabolic syndrome was diagnosed according to the International Diabetes Federation criteria. RESULTS: The frequency of metabolic syndrome was 58.3%. The comparison of the lipidic parameters between subject with and without metabolic syndrome showed a significant increase in ApoB and NHDL-C but not in LDL-C. By considering triglyceride (TG) limits (TG ≤ 0.9 mmol/L and TG > 1.70 mmol/L), we noted no differences in ApoB, NHDL-C, and LDL-C between subjects with and without metabolic syndrome in triglyceridemia ≤0.9 mmol/L. In triglyceridemia >1.70 mmol/L, a significant increase in ApoB and NHDL-C, but not in LDL-C, was noted. These results seem to consolidate the probability of increased sd-LDL in hypertriglyceridemic metabolic syndrome subjects. Indeed, in our study the odds ratio (OR) of SCS associated with metabolic syndrome is 3.81 (P = 0.007) in the studied population. This risk increases to 8.70 (P = 0.026) in hypertriglyceridemic subjects and seems to be associated with ApoB and NHDL-C (OR = 1.87, P = 0.038; OR = 1.26, P = 0.048). CONCLUSIONS: This study suggests that ApoB and NHDL-C seem to be more correlated to SCS in metabolic syndrome with hypertriglyceridemia than LDL-C.

Elevated liver enzymes in metabolic syndrome are associated with coronary stenosis in a Tunisian population.

BACKGROUND: Recently, elevated liver enzymes have attracted great interest as potential novel markers of cardiovascular risk. The aim of this study was to investigate if there is a relationship between elevated liver enzymes and coronary stenosis associated with metabolic syndrome in a Tunisian population. METHODS: We enrolled 192 patients who underwent coronary angiography. Significant coronary stenosis (SCS) was diagnosed in the presence of coronary stenosis with lumenal narrowing >or=50%. Metabolic syndrome was defined according to the International Diabetes Federation criteria. RESULTS: Frequencies of subjects with liver enzyme activities belonging to quartile 4 were higher in the group with metabolic syndrome. Association of SCS with metabolic syndrome was more significant in the quartile 4 of gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT). Odds ratios of SCS associated with metabolic syndrome were: [1.40 (0.66-2.9) for quartile 1 versus 4.20 (1.3-9.9) for quartile 4 of GGT; 1.52 (0.29-3.7) for quartile 1 vs. 5.30 (1.39-18.9) for quartile 4 of ALT]. CONCLUSIONS: Elevated liver enzyme activity was associated with metabolic syndrome and only GGT and ALT seem to be associated with an increase of the coronary stenosis in the studied population with metabolic syndrome.

5' ins/del and 3' VNTR polymorphisms in the apolipoprotein B gene in relation to lipids and coronary artery disease.

BACKGROUND: Studies that considered apolipoprotein B (APOB) gene polymorphisms as risk factors for coronary artery disease (CAD) have reported conflicting results. We sought to analyze the association between 5' ins/del and 3' VNTR polymorphisms of APOB, lipid parameters and CAD risk. METHODS: We recruited 251 patients with CAD, documented by coronary angiography, and 94 controls. Genotyping was performed by PCR. Lipids and apolipoproteins were measured. RESULTS: 5' ins/del (ins/ins, ins/del, del/del) and 3' VNTR (LL, SS, LS) polymorphism frequencies were significantly (p<0.05) different between controls and CAD patients. LL and del/del were significantly associated with higher levels of apolipoprotein B (apoB), total cholesterol/high-density lipoprotein cholesterol ratio and apoB/apoA-I ratio (p<0.05) and with increased risk of CAD. The odds ratio for significant coronary stenosis associated with del/del was 3.2 (95% CI 1.6-36.42) (p=0.032) and with LL was 2.2 (95% CI 1.1-5.1) (p=0.042). CONCLUSIONS: The two polymorphisms exert an impact on lipid levels and contribute to the susceptibility to the development of CAD.

Association of the cholesteryl ester transfer protein Taq1 B2B2 genotype with higher high-density lipoprotein cholesterol concentrations and lower risk of coronary artery disease in a Tunisian population.

BACKGROUND: The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is undergoing debate. AIMS: In this prospective study, we sought to explore the role of the CETP Taq1B variant in coronary artery disease risk, and its association with plasma lipid and apolipoprotein concentrations. METHODS: DNA was extracted from 316 patients undergoing coronary angiography. The Taq1B polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis. Lipid and apolipoprotein concentrations were measured by enzymatic and nephelometric assays. RESULTS: In our study population, the B2 allele frequency was 0.29. B2 allele carriers had a significantly higher high-density lipoprotein cholesterol (HDL-C) concentration than those with the B1B1 genotype (1.041+/-0.294 versus 0.995+/-0.277; p=0.039). After adjusting for age, sex, smoking status, diabetes, hypertension and dyslipidaemia, the odds ratio (OR) for significant stenosis associated with the B2 allele was 0.82 (95% confidence interval (CI) 0.60-0.97; p=0.039), suggesting that the B2 allele is associated with an 18% lower risk of significant stenosis. This protective effect seemed to be more significant in male nonsmokers (38% lower risk; OR 0.62, 95% CI 0.29-0.92; p=0.029). No significant protective effects were observed in women or male smokers. CONCLUSION: Our data suggest that the B2 allele is associated with higher concentrations of HDL-C, which confer a protective effect with regard to coronary atherosclerosis. This effect seems to be more significant in men than in women and in nonsmokers than in smokers.