Mohamed Hédi Sbaï

The paraoxonase L55M and Q192R gene polymorphisms and myocardial infarction in a Tunisian population.

OBJECTIVES In the present study, we examined a possible association between the PON1 Q192R and L55M polymorphisms and myocardial infarction (MI) in a sample of the Tunisian population. DESIGN AND METHODS Three hundred and ten patients with MI and 375 controls were recruited. Paraoxonase gene polymorphisms at codon 192 and 55 were analyzed by PCR-RFLP. RESULTS Genotype distributions and allele frequencies of L55M were similar among the control and MI groups. For the Q192R polymorphism patients with MI had significantly higher frequency of the RR genotype compared to controls [17.1% vs. 10.9%; OR (95% CI), 1.93 (1.24-3.02); p=0.004]. The MI patient group showed a significantly higher frequency of the R allele compared to the controls [38% vs. 30%; χ(2)=10.74, p=0.001]. The association between the PON1 Q192R polymorphism and MI remained significant after adjustment for other well-established cardiovascular risk factors. CONCLUSIONS The present study showed a significant and independent association between the PON1 Q192R polymorphism (presence of R allele) and MI in the Tunisian population.

Polymorphisms of the NOS3 gene and risk of myocardial infarction in the Tunisian population.

Controversial results regarding the association of eNOS gene (NOS3) polymorphisms with myocardial infarction (MI) have been reported. This study investigated the relationship of the -786T>C (rs2070744), 894G>T (rs1799983) and 4a4b polymorphisms of the NOS3 gene with the presence of MI in the Tunisian population. In addition, we also examined the association of NOS3 gene haplotypes with MI in Tunisian subjects. A total of 303 patients with MI and 225 controls were included in the study. The 894G>T and -786T>C single nucleotide polymorphisms were analyzed by PCR-RFLP, and 4a4b polymorphism just for PCR. There was significant linkage disequilibrium between the three NOS3 polymorphisms (p<0.0001). The genotype distribution and allele frequency of NOS3 4a4b, but not -786T>C and 894G>T, polymorphism was significantly different between MI patients and controls. The univariate logistic regression analysis showed a significant association of the 4a4b polymorphism and MI according to co-dominant, dominant and recessive models (co-dominant model OR: 4.38, 95%CI: 1.24-15.41; p=0.021, dominant model OR: 1.66, 95%CI: 1.14-2.42); p=0.007, and recessive model OR: 3.85, 95%CI: 1.10-13.47; p=0.035). The multivariate analysis, adjusted for traditional cardiovascular risk factors, revealed that the NOS3 4a4a genotype was an independent predisposing factor to MI, according to the models considered. In addition, a haplotype 7 (C-T-4a), (OR=12.05, p=0.010) was a risk factor of MI after controlling for classical risk factors. These finding suggest that the 4a4b polymorphism of the NOS3 gene was associated with MI in Tunisian patients.

Association between paraoxonase-1 gene promoter -108C/T polymorphism and myocardial infarction in the Tunisian male population / Tunuslu erkek populasyonunda miyokard enfarktüs ile paraoksonaz -1 gen başlatıcı -108C/T polimorfizmi arasındaki ilişki

Abstract Objective: Human paraoxonase 1 (PON1) is an HDL-associated enzyme with anti-oxidant/anti-inflammatory properties that has been suggested to play an important protective role against coronary artery disease (CAD). The PON1 promoter -108C/T polymorphism has been analyzed in numerous association studies as a genetic marker for CAD, however, with controversial results. The aim of this study was to evaluate the association of PON-1 promoter -108C/T polymorphism with the risk of myocardial infarction (MI) in the Tunisian male population. Methods: A total of 815 subjects were recruited, including 318 healthy controls and 497 MI patients. Genotypes were determined by PCR-RFLP method. Genotype/allele frequencies were compared in patients and controls using the chi-square test. Results: Genotype distributions and allele frequencies of PON-1 promoter -108C/T polymorphism were different among the control and MI groups. Patients with MI had significantly higher frequency of the TT genotype compared to controls [29.2% vs. 25.5%; OR (95% CI), 1.67 (1.52-2.49); p=0.010]. The MI patient group showed a significant higher frequency of the T allele compared to the controls [0.56 vs. 0.51; χ2=8.61, p=0.013]. The association between the PON-1 promoter -108C/T polymorphism and MI remained significant after adjustment for other well-established cardiovascular risk factors. Conclusion: The present study showed a significant and independent association between the PON-1 promoter -108C/T polymorphism and MI in the Tunisian male population. Özet Amaç: İnsan paraoksanaz enzimi 1 (PON1), anti oksidan/anti enflamatuar ozelliği olan HDL-ilişkili bir enzim olup koroner arter hastalıklarında (CAD) onemli koruyucu rol oynamakta olduğu bildirilmektedir. PON 1 başlatıcı -108C/T polimorfizmi ceşitli ilişkilendirme calışmalarında analiz edilmiş CAD icin bir genetic marker olarak saptanmış olamakla birlikte celişkili veriler de bulunmaktadır. Bu calışmanın amacı PON1 başlatıcı -108C/T polimorfizminin miyokard enfarktus (ME) riski ile ilişkisinin Tunus’lu erkek populasyonunda değerlendirilmesidir. Metod: Calışma kapsamında 318 normal ve 497 ME hastası olmak uzere toplam 815 birey incelenmiştir. Genotipler PCR-RFLP metodu ile belirlenmiştir. Kontrol ve hasta genotip/alel frekans karşılaştrmaları chi-kare testi kullanılarak yapılmıştır. Bulgular: Kontrol ve MI hasta grupları arasında, PON-1 başlatıcı -108C/T polimorfizmi genotip dağılımları ve alel frekansları farklı olarak bulundu. ME hastalarında TT genotipi kontrole gore anlamlı olarak yuksek idi [29.2% vs. 25.5%; OR (95% CI), 1.67 (1.52-2.49); p=0.010]. Ayrıca, ME hasta grubunda T alel frekansı da kontrol grubuna gore anlamlı olarak yuksek bulundu [0.56 vs. 0.51; χ2=8.61, p=0.013]. PON-1 başlatıcı -108C/T polimorfizmi ve MI arasındaki ilişki diğer iyi tanımlanmış kardiyo vaskuler hastalık faktorlerine gore duzeltmeler yapıldığında da anlamlı olarak yuksek bulundu. Sonuç: Bu calışma Tunuslu erkek populasyonunda, PON-1 başlatıcı -108C/T polimorfizmi ve ME arasında anlamlı ve bağımsız ilişki olduğunu gostermektedir.

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

Background & objectives: The impact of several environmental and genetic factors on diabetes is well documented. Though the association between the vitamin D receptor (VDR) gene polymorphisms and type 2 diabetes mellitus (T2DM) has been analyzed in different ethnic groups, the results have been inconsistent. The aim of this study was to evaluate the possible association between VDR FokI polymorphism and genetic susceptibility to T2DM in Tunisian population. Methods: A total of 439 unrelated patients with T2DM and 302 healthy controls were included in the study. Genomic DNA was extracted from blood and genotyped for the single nucleotide polymorphism (SNP) of FokI (T/C: (rs2228570) by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. Results: The genotype distribution and the relative allelic frequencies for the FokI polymorphism were not significantly different between T2DM and controls: in T2DM patients the frequencies of the CC, CT, and TT genotypes were 52.6, 41.0, and 6.1 per cent, respectively, and in controls the genotype frequencies were 55.6, 38.7, and 5.6 per cent, respectively. In our study, the TT genotype of the FokI polymorphism was not associated with T2DM (OR =1.19, 95% CI 0.63 - 2.25, P=0.577). Interpretation & conclusions: Our study showed no significant association of the FokI polymorphism in the vitamin D receptor gene with type 2 diabetes mellitus in Tunisian population.

0185: Prevalence of conventional risk factors in 44154 Tunisians patients with coronary heart disease

Introduction The prevalence of the major conventional cardiovascular risk factors (cigarette smoking, diabetes mellitus, hypertension, and dyslipidemia) among coronary heart disease (CHD) patients in Tunisia has not been studies extensively. The aim of this study was to evaluate the frequency of cardiovascular risk factors and their association in patients hospitalised for coronary heart disease at Rabta, charles Nicolle, Habib Thameur, Military Hospitals (Tunis), Fattouma Bourguiba hospital (Monastir), Farhat Hached, and Sahloul hospitals (Sousse); Mohamed Tahar Maamouri Hospital (Nabeul); Menzel Bourguiba Hospital and Ibn El Jazzar Hospital (Kairouan) over the period 1994-1998 and during 2004. Methods The clinical features of 44154 patients (25635 men (58.1%) and 18519 women (41.1%) on hospital admission were analyzed. Results 40.8% of the patients were hospitalized for coronary deficiency, 16.5% for valvular cardiopathy, 4.8% for cardiomiopthy, 16.9% for arrhythmia and conduction disturbance, 3.6% for essential hypertension, 2.5% for stroke and 14.9% for various pathologies. The prevalence of hypertension, diabetes, smoking, obesity and dyslipidemia was 29.9%, 30.3%, 66.9%, 11.9%, and 30.2% respectively in the men and 43.5%, 30.2%, 3.5%, 14.6%, and 27.1% respectively in women. Conclusion With this risk factor profile Tunisia has to implement a national strategy of primary prevention and heart health promotion in addition to the efforts recently made in secondary prevention of some chronic disease such as hypertension, diabetes, and smoking.

0183: A common polymorphism in CD40 Kozak sequence (-1C/T) is associated with myocardial infraction in the Tunisian male population

Background Coronary artery disease is influenced by both environmental and genetic factors. Current evidence shows that the CD40-CD40 ligand (CD40-CD40L) system plays a crucial role in the development, progression and outcome of acute coronary syndrome. A single nucleotide polymorphism (SNP) located at position –1 in the Kozak sequence of the CD40 gene (rs1883832; C>T) has been associated with the development of acute coronary syndrome. The purpose of the study was to explore the association between the C/T (–1) single nucleotide polymorphism in the CD40 gene and myocar-dial infarction (MI) in the Tunisian male population. Methods A total of 273 unrelated Tunisian patients with MI and 219 healthy controls were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Clinical parameters such as fasting serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, and plasma glucose were detected by autoanalyzer assay. Weight, height and blood pressure (BP) were measured and body mass index (BMI) was calculated. Results Patients with MI had significantly higher frequency of the TT genotypes compared to controls (12.5% vs. 5.9%; OR=1.43, 95% CI: 1.08 – 1. 89, p=0.011). The MI patient group showed a significant higher frequency of the T allele compared to the controls (0.33 vs. 0.26; OR=1.45, 95% CI: 1.09 – 1.94, p=0.008). The association between the C/T (–1) single nucleotide polymorphism in the CD40 gene and MI remained significant after adjustment for other well-established cardiovascular risk factors. Conclusion Our study suggests that C/T (–1) single nucleotide polymorphism in the CD40 gene might contribute to the susceptibility to MI in the Tunisian male population. Further replication with larger numbers, and populations of different ethnicities, are needed to confirm our finding.

0184: Genetic association between single nucleotide polymorphisms in the Paraoxonase 1 (PON1) gene and the risk of myocardial infarction in the Tunisian male population

Background Coronary artery disease (CAD), the leading cause of death worldwide, is a multifactorial disease arising from the complex interplay of genetic and environmental factors. Paraoxonase 1 (PON1) polymorphisms have been implicated as risk factors for CAD, but the results of genetic association studies on the related phenotype of CAD are inconclusive. The aim of the present study was to investigate the association between the PON1 promoter –108 C>T (rs705381) and the coding region Gln192Arg (Q192R, rs662) and Leu55Met (L55M, rs854560) variants with myocardial infarction (MI) in a sample of the Tunisian population. Methods A total of 382 unrelated MI patients and 380 healthy controls were enrolled in this study. Genotyping was performed by the polymerase chain reaction and restriction fragment length polymorphism method (PCRRFLP). The frequencies of the alleles and genotypes between MI patients and controls were compared by the chi-square test. Results Genotype distribution and allele frequencies of L55M were similar among the control and MI groups. The PON1-Q192R and –108 C>T genotypes exhibited significant differences in allele and genotype frequencies among the MI and control groups. At PON1-192 locus, there were significant differences between patients and controls (p T polymorphism was found to be a risk marker for MI (OR=1.29, CI: 1.05 – 1.58; p=0.011). Conclusions The present study showed a significant and independent association between the PON1 Q192R and – 108 C>T polymorphisms and MI in the Tunisian male population.

0501: Association of Cys311Ser polymorphism of paraoxonase-2 gene with myocardial infarction in the Tunisian male population

Introduction Paraoxonase 2 (PON2) has antioxidant properties similar to paraoxonase-1 and paraoxonase-3. However, in contrast to paraoxonase-1 and paraoxonase-3, paraoxonase-2 is not associated with high-density lipoproteins and may only exert its antioxidant function at the cellular level. PON2 may also play a role in the pathogenesis of arterial thrombosis and atherosclerosis. The purpose of the present study was to investigate the possible association between the Cys311Ser polymorphism of PON2 gene and myocardial infarction (MI) in the Tunisian male population Materials and methods A total of 700 unrelated Tunisian subjects including 321 patients with MI and 379 healthy controls were included in this study. Genomic DNA was extracted from peripheral blood leukocytes according to standard methods. PON2 genotypes were determined by PCRRFLP method. Results A significant difference in genotype distribution and allele frequencies was observed between MI patients and controls. Patients with MI had a frequency of 17.1% for CC genotype, 45.8% for the CS genotype and 37.1% for the SS genotype. The controls had a frequency of 26.1% for the CC genotype, 45.6% for the CS genotype and 28.2% for the SS genotype (χ 2 =10.58; p=0.005). The MI patient group showed a significantly higher frequency of the S allele compared to the controls (0.60 vs 0.51; χ 2 =11.16; p Conclusion Our results showed a significant and independent association between the PON2 C311S polymorphism (presence of S allele) and MI in the Tunisian male population.