Nabila Ben Rejeb

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.

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.

Association Between Eight Adiponectin Polymorphisms, Obesity, and Metabolic Syndrome Parameters in Tunisian Volunteers

BACKGROUND Adiponectin is a plasma protein produced by the adipose tissue, with insulin sensibility, antiinflammatory and antiatherogenic properties. Many adiponectin gene polymorphisms have been described, and their implication in obesity, metabolic syndrome, and cardiovascular diseases was controversial. Our aim was to study the relationship between eight adiponectin polymorphisms (-1391G/A, -1377C/G, 4522C/T, 395 G/A, 276G/T, 639C/T, 45T/G, and +2019delA), metabolic syndrome parameters, and the risk of obesity in Tunisian volunteers. METHODS We have 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 (BMI≥30 kg/m(2)) (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 (PCR-RFLP). Glucose, insulin, and lipids were measured. BMI and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. RESULTS The polymorphisms 276G/T, 639 C/T, 11391 G/A, 11374C/G, and +2019delA seem to contribute to obesity. In fact, adjusted odds ratios (ORs) of obesity associated with mutated genotypes of each polymorphism were, respectively: OR=0.64, P=0.039; OR=1.85, P=0.018; OR=1.68, P=0.044; OR=1.77, P=0.038; and OR=1.94, P=0.010). Mutated genotypes at 639 C/T were associated with higher waist circumference, BMI, and systolic and diastolic blood pressure. In addition, the 11391AA genotype was associated with increased BMI. Concerning 2019delA, the delAdelA genotype was associated with increased HOMA-IR and BMI, suggesting a possible effect of these single-nucleotide polymorphisms (SNPs) on insulin resistance parameters. Mutated genotypes at 276G/T were associated with lower serum insulin concentration and lower systolic and diastolic blood pressure. The other genotypes showed no association with metabolic syndrome parameters. CONCLUSION Adiponectin gene polymorphisms were associated with obesity and metabolic syndrome parameters 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.

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

Abstract 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. Clin Chem Lab Med 2008;46:329–34.

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.

Four polymorphisms of cholesteryl ester transfer protein gene and coronary stenosis in a Tunisian population

Aims The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is under debate. We studied the association of four polymorphisms (Taq1B, I405V, R451Q and A373P) in the CETP gene with lipid profile and coronary artery disease. Methods Four CETP polymorphisms were studied in 316 Tunisian patients undergoing coronary angiography. Patients were clinically examined and their lipid profiles were estimated. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. Results The 451Q allele, associated with lower high-density lipoprotein-cholesterol (HDL-C) and higher total cholesterol and apolipoprotein B (ApoB) concentrations, was also significantly associated with an increased risk of significant stenosis [odds ratio (OR) = 1.74, 95% confidence interval (CI) 1.15–2.61, P = 0.007]. The B2 allele of Taq1B polymorphism had an increase in HDL-C concentration and was associated with a decreased risk of coronary stenosis, as described earlier. It was also associated with low risk of hypoHDLaemia [OR = 0.615, 95% CI 0.377–1.002, P = 0.035]. No significant effect of different A373P and I405V alleles was found on the lipid profile and on coronary stenosis. When CETP polymorphisms were combined in haplotypes possessing R451Q, A373P, I405V, Taq1B polymorphisms, the 1112 haplotype (where 1 is the wild genotype and 2 represents carriers of the variant allele) seems to be the most protective against significant stenosis (OR = 0.71, 95% CI 0.188–0.983; P = 0.014), whereas 2111 was probably the most atherogenic, with an OR = 2.17, 95% CI 1.06–5.88; P = 0.039. Conclusion The Q allele of the R451Q polymorphism was associated with decreased HDL-C, increased ApoB concentrations and increased risk of coronary stenosis. In haplotype analysis, we found that 1112 seems to be a protective haplotype, whereas 2111 has an atherogenic effect in a coronary Tunisian population.

Association of three polymorphisms of scavenger receptor class BI gene (exon8, exon1, intron5) with coronary stenosis in a coronary Tunisian population.

BACKGROUND The potential role of scavenger receptor class BI (gene name SCARB1) in the regulation of lipoproteins metabolism and atherosclerosis has attracted considerable interest. We tested the relationship of SCARB1 polymorphisms with significant coronary stenosis (SCS) and lipid profile in a coronary Tunisian population. METHODS Three SCARB1 polymorphisms (exon8 (C/T), exon1 (G/A), intron5 (C/T)) were studied in 316 Tunisian patients undergoing coronary angiography. SCS was defined as a luminal narrowing of ≥ 50% in at least one major coronary artery. Lipid profile was measured. Genotyping was performed using PCR-RFLP. RESULTS Individuals with TT genotypes of exon8 were associated with higher concentrations of plasma HDL-C and ApoAI in the group without SCS. Carriers of T allele of exon8 were associated with 41% lower risk of SCS. This protective effect seemed to be particularly significant in women, nondiabetics and nonsmokers. Subjects homozygous for the variant allele of intron5 were significantly associated with an increased risk of SCS, particularly in smokers. AA genotype of exon1 was associated with an increased risk of SCS in diabetics and in patients with metabolic syndrome. The (CAT) haplotype was associated with increase in the risk of SCS compared to the wild haplotype and had a 4-fold greater risk of SCS than patients with haplotype (TGC) which seems to be the most protective against SCS. CONCLUSION Carriers of T allele of exon8 in SCARB1 seemed to increase HDL-C and ApoAI concentrations and reduce the risk of SCS. The intron5, exon1 and (CAT) haplotype seemed to have an atherogenic effect.

Metabolic syndrome is a risk factor for coronary artery disease in a tunisian population.

BACKGROUND Metabolic syndrome is a constellation of disorders that produces a high risk of atherosclerosis. The prevalence of metabolic syndrome clearly varies depending on ethnicity. The aim of this study was to investigate the prevalence of metabolic syndrome and its relationship with significant coronary stenosis (SCS) in a Tunisian population. METHODS Metabolic syndrome was diagnosed according to the International Diabetes Federation criteria. SCS was defined as a luminal narrowing of more or equal to 50% in at least 1 major coronary artery, as judged by coronary angiography. A total of 192 subjects documented by coronary angiography were recruited from the cardiology department. RESULTS In all, 54.2% (n = 104) of patients presented with metabolic syndrome, with a higher prevalence among women (65.9% vs. 45.5%; P = 0.004). In the subjects with metabolic syndrome, the fasting hyperglycemia was the most common metabolic disorder (86.5%). The risk of SCS increased approximately 3-fold in the presence of metabolic syndrome [odds ratio (OR) = 3.38, P = 0.004]. In addition, SCS risk was increased according to the increase in the number of metabolic syndrome components. The most atherogenic profile was that which assembled five metabolic syndorme components (OR = 4.18, P = 0.001). There was a significant relationship between the homeostasis model of insulin resistance (HOMA-IR) and the risk of SCS in the presence of metabolic syndrome. In fact, the OR of SCS associated with metabolic syndrome was (4.96, P = 0.001) in participants in the highest quartile of HOMA-IR. CONCLUSIONS This study suggests that metabolic syndrome is a risk factor for SCS. The detection, prevention, and treatment of the underlying risk factors of metabolic syndrome should become an important approach for reduction of the cardiovascular disease burden in our study population.

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.