RESUMO
BACKGROUND: Adipose tissue is an important endocrine organ that secretes a number of adipokines, like Resistin (RETN); it's an adipocytes-secreted cytokine and has been proposed as a link between obesity and diabetes. Many resistin gene polymorphisms were described and their implication in obesity was controversial. This study was to investigate the prevalence of single nucleotide polymorphisms (SNPs) in RETN gene 420C/G; 44G/A; 62G/A; 394C/G and 299 G/A and their association with Resistin level and obesity in Tunisian volunteers. METHODS: We recruited 169 nonobese (mean age=42.16-14.26 years; mean body mass index [BMI]=24.51-3.69 kg/m2 ) and 160 obese (mean age=47.86-11.17 years; mean BMI=36-4.78 kg/m2 ). Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism. Anthropometric parameters, lipid levels, Glycemia and insulinemia were measured, BMI was calculated and insulinresistance was evaluated with the homeostasis model assessment insulin resistance (HOMA-IR) and resistin level was measured by ELISA. Statistical analyses were performed by SPSS19.0. RESULTS: After adjustment for confounding parameters; the Odds Ratio (OR) of obesity associated with mutated genotypes at 420C/G compared with normal genotype was as: OR=2.17; 95% CI [1.28-3.68], P=.004. The serum Resistin levels present no significant association with all RETN polymorphisms and it was significantly associated with BMI (P=.047). In our haplotype analysis, one haplotype seems to be protective and one other seems to be the highest risk to obesity. CONCLUSION: The 420 C/G Polymorphism were associated with obesity and Leptin concentration in our population.
Assuntos
Obesidade , Resistina/sangue , Resistina/genética , Adulto , Feminino , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/epidemiologia , Obesidade/genética , Polimorfismo de Nucleotídeo Único/genética , Curva ROC , Fatores de Risco , Tunísia/epidemiologiaRESUMO
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 (+45TAssuntos
Adiponectina/genética
, Predisposição Genética para Doença/genética
, Leptina/genética
, Obesidade
, Polimorfismo de Nucleotídeo Único/genética
, Receptores para Leptina/genética
, Resistina/genética
, Adulto
, Antropometria
, Feminino
, Frequência do Gene
, Haplótipos
, Humanos
, Masculino
, Pessoa de Meia-Idade
, Obesidade/epidemiologia
, Obesidade/genética
, Razão de Chances
, Prevalência
RESUMO
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.
Assuntos
Doença da Artéria Coronariana/genética , Haptoglobinas/genética , Idoso , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/fisiopatologia , Estenose Coronária/genética , Estenose Coronária/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/genética , Polimorfismo Genético , Índice de Gravidade de Doença , Fumar/genética , TunísiaRESUMO
Gestational diabetes mellitus (GDM) is pathology of glucose intolerance during pregnancy. It is influenced by maternal hyperglycemia and insulinemia through placental circulation. The study was undertaken to investigate the implication of pro-inflammatory factors in the placenta of GDM women. Thirty GDM women have delivered macrosomic babies, and 30 healthy age-matched pregnant women have delivered non macrosomic babies, were recruited in the study. The mRNAs encoding for IL-6, TLR4, TGF-ß, CD68, CD14, EMR-1, CCL2, TCR-α, T-bet, GATA-3, leptin and adiponectin were quantified in placental samples by using RT-qPCR. The mRNA expression of the pro-inflammatory factors, i.e., IL-6, TLR4 and TGF-ß, was increased in GDM placenta. The mRNA expression of markers of infiltration of macrophage, i.e., CD68, CD14 and EMR-1, was higher in the GDM placenta than the control placenta. The expression of mRNA of TCR-α, an indicator of T-cell infiltration, was significantly higher in the GDM placenta. Interestingly, the expression of mRNA of GATA-3, an indicator of Th2 phenotype differentiation, was unregulated in the GDM placenta. Leptin and adiponectin mRNAs were also significantly increased in the placenta of the GDM group. Our results revealed that there is an increase of inflammation in the GDM placenta which might be involved, in part, in the pathogenesis of macrosomia.
Assuntos
Diabetes Gestacional/metabolismo , Placenta/metabolismo , Adolescente , Adulto , Biomarcadores/metabolismo , Glicemia/metabolismo , Diabetes Gestacional/sangue , Feminino , Regulação da Expressão Gênica , Hemoglobinas Glicadas/metabolismo , Humanos , Inflamação/genética , Inflamação/metabolismo , Insulina/sangue , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Adulto JovemRESUMO
BACKGROUND: To evaluate whether abnormal endothelial function, a common finding in gestational diabetes mellitus (GDM) pregnancies, can be explained by inflammatory cytokines. METHODS: Forearm skin blood flow (FSBF), into response to acetylcholine (Ach) (endothelium-dependent vasodilatation), were measured in 24 pregnant control subjects and 28 gestational diabetes mellitus (GDM) women, in the third trimester of gestation. A fasting glycemic and lipidic panel was obtained, and inflammatory cytokines (TNF-α and IL-6) and adiponectin were also determined. RESULTS: FSBF is significantly reduced in GDM group compared with control subjects (344.59 ± 57.791 vs.176.38 ± 108.52, P < 0.05). Among all subjects, FSBF showed a strong negative correlation with TNF-α and IL-6 (r = -0.426, P < 0.0001 and r = -0.564, P < 0.0001, respectively) and positive correlation with adiponectin (r = 0.468, P < 0.0001). CONCLUSIONS: Endothelial function, an early marker of macrovascular disease, is present in non-obese pregnancies complicated by GDM. This alteration seems to be directly related to inflammatory status, which may represent a patho-physiological link between GDM and type 2 diabetes and, later on, metabolic syndrome.
Assuntos
Diabetes Gestacional/sangue , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Inflamação/fisiopatologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Acetilcolina/administração & dosagem , Adiponectina/sangue , Adulto , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Gestacional/fisiopatologia , Fatores Relaxantes Dependentes do Endotélio/administração & dosagem , Feminino , Antebraço/irrigação sanguínea , Humanos , Inflamação/sangue , Interleucina-6/sangue , Síndrome Metabólica/sangue , Síndrome Metabólica/fisiopatologia , Obesidade/patologia , Gravidez , Fator de Necrose Tumoral alfa/sangue , VasodilataçãoRESUMO
PON1 and PON2 have attracted considerable attention as candidate genes for coronary heart disease because their enzymes function as key factors in lipoprotein catabolism pathways. We studied the distribution of PON1 and PON2 polymorphisms, including genotyping, lipid profile, and PON1 activity, and their association with PON1 activity and significant coronary stenosis (SCS) in a Tunisian population. PON1 activity was lower in patients with SCS than in controls. It increased with the R allele (QQ < QR < RR) in PON1-192 genotypes and with the L allele (MM < ML < LL) in PON1-55 genotypes. In the presence of metabolic syndrome and diabetes, PON1-192RR and PON2-311CC were associated with an increased risk of SCS and PON1-55MM seems to have lower risk. This association was evident among nonsmokers for PON1-55MM and among smokers for PON1-192RR and PON2-311CC. The GTGC haplotype seemed to increase the risk of SCS compared with the wild haplotype in a Tunisian population.
Assuntos
Arildialquilfosfatase/genética , Estenose Coronária/enzimologia , Adulto , Idoso , Sequência de Bases , Estenose Coronária/genética , Primers do DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , TunísiaRESUMO
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.
Assuntos
Estenose Coronária/genética , Lipase Lipoproteica/genética , Polimorfismo Genético , Idoso , Apolipoproteína A-I/genética , Apolipoproteínas B/genética , Doença da Artéria Coronariana/genética , Estenose Coronária/etnologia , Feminino , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Lipídeos/genética , Lipase Lipoproteica/sangue , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , TunísiaRESUMO
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.
Assuntos
Estenose Coronária/genética , Éxons , Íntrons , Receptores Depuradores Classe B/genética , Idoso , Feminino , Predisposição Genética para Doença , Haplótipos , Heterozigoto , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , TunísiaRESUMO
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.
Assuntos
Síndrome Metabólica/genética , Obesidade/genética , Polimorfismo Genético , Receptores para Leptina/genética , Adulto , Substituição de Aminoácidos , Glicemia/metabolismo , Índice de Massa Corporal , Colesterol/sangue , Ingestão de Energia/genética , Feminino , Haplótipos , Humanos , Insulina/sangue , Leptina , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/epidemiologia , Receptores para Leptina/sangue , Fatores de Risco , TunísiaRESUMO
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.
Assuntos
Predisposição Genética para Doença , Síndrome Metabólica/genética , Obesidade/genética , Polimorfismo Genético , Resistina/genética , Adulto , Índice de Massa Corporal , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , TunísiaRESUMO
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)â=â1.74, 95% confidence interval (CI) 1.15-2.61, Pâ=â0.007]. 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 [ORâ=â0.615, 95% CI 0.377-1.002, Pâ=â0.035]. 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 (ORâ=â0.71, 95% CI 0.188-0.983; Pâ=â0.014), whereas 2111 was probably the most atherogenic, with an ORâ=â2.17, 95% CI 1.06-5.88; Pâ=â0.039. 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.
Assuntos
Proteínas de Transferência de Ésteres de Colesterol/genética , Estenose Coronária/genética , DNA/genética , Predisposição Genética para Doença , Polimorfismo Genético , Alelos , Apolipoproteínas B/sangue , Aterosclerose/sangue , Aterosclerose/epidemiologia , Aterosclerose/genética , Proteínas de Transferência de Ésteres de Colesterol/sangue , HDL-Colesterol/sangue , Intervalos de Confiança , Estenose Coronária/sangue , Estenose Coronária/epidemiologia , Feminino , Frequência do Gene , Genótipo , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Razão de Chances , Reação em Cadeia da Polimerase , Estudos Prospectivos , Fatores de Risco , Tunísia/epidemiologiaRESUMO
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 (GGâ+âTG) were associated with an increase in SCS only in the obese group. Mutated genotypes at +276G/T (TTâ+âGT) 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.
Assuntos
Estenose Coronária/genética , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Adiponectina/genética , Idoso , Angiografia Coronária , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/epidemiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Razão de Chances , Fenótipo , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Tunísia/epidemiologiaRESUMO
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.
Assuntos
Síndrome Metabólica/genética , Obesidade/genética , Polimorfismo Genético/fisiologia , Adiponectina/genética , Adulto , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Experimentação Humana , Humanos , Masculino , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição/fisiologia , Polimorfismo de Nucleotídeo Único/fisiologia , Fatores de Risco , Deleção de Sequência/fisiologia , TunísiaRESUMO
BACKGROUND: The adenosine triphosphate-binding cassette transporter A1 (ABCA1) protein plays an important role in the first step of the reverse cholesterol transport system. AIMS: We studied the association of four polymorphisms in the ABCA1 gene (G1051A, G2706A, G2868A and -565C/T) with lipid profile and coronary artery disease. METHODS: Overall, 316 Tunisian patients underwent coronary angiography. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. Lipid and apolipoprotein concentrations were measured. RESULTS: Only carriers of the G2706A allele were associated with a decreased risk of significant stenosis (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.22-0.92, p = 0.029), without pronounced effects on high-density lipoprotein (HDL) cholesterol. This protective effect was significant in smokers and diabetes. Carriers of the G1051A allele were associated only with increased concentrations of HDL cholesterol (p = 0.032). G2868A and -565C/T did not show any association with lipids or risk of significant stenosis. When ABCA1 polymorphisms were combined in haplotypes possessing G1051A, G2706A, G2868A and -565C/T, (AAGC) seemed to be most protective against significant stenosis (OR 0.5, 95% CI 0.29-0.96, p = 0.048) whereas (GGAT) was probably the most atherogenic (OR 1.26, 95% CI 1.03-1.56, p = 0.025). CONCLUSION: Only the G2706A allele seems to be associated with a reduced risk of significant stenosis without important modification of HDL-cholesterol concentration, and appears to be more protective for smokers and diabetic patients. We found that (AAGC) seems to be a protective haplotype whereas (GGAT) has an atherogenic effect in a Tunisian population.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , População Negra/genética , Estenose Coronária/genética , Polimorfismo de Nucleotídeo Único , Transportador 1 de Cassete de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/metabolismo , Idoso , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Angiografia Coronária , Estenose Coronária/sangue , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/etnologia , Complicações do Diabetes/etnologia , Complicações do Diabetes/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Desequilíbrio de Ligação , Lipídeos/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Reação em Cadeia da Polimerase , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fumar/efeitos adversos , Tunísia/epidemiologiaRESUMO
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.
Assuntos
Apolipoproteínas B/sangue , LDL-Colesterol/sangue , Doença da Artéria Coronariana/diagnóstico , Hipertrigliceridemia/diagnóstico , Síndrome Metabólica/diagnóstico , Idoso , Biomarcadores/análise , Biomarcadores/sangue , HDL-Colesterol/sangue , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/complicações , Feminino , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/complicações , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Modelos Biológicos , Concentração Osmolar , Prognóstico , Fatores de RiscoRESUMO
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.
Assuntos
Doença da Artéria Coronariana/etiologia , Síndrome Metabólica/complicações , Idoso , Doença da Artéria Coronariana/epidemiologia , Estenose Coronária/complicações , Estenose Coronária/epidemiologia , Feminino , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , População , Prevalência , Fatores de Risco , Tunísia/epidemiologiaRESUMO
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.