Contribution of the ACE (rs1799752) and CYP11B2 (rs1799998) Gene Polymorphisms to Atrial Fibrillation in the Tunisian Population.

BACKGROUND: This study investigated the association of angiotensin-converting enzyme (ACE I/D) and aldosterone synthase (CYP11B2-344C/T) gene polymorphisms in the renin-angiotensin-aldosterone system (RAAS) with atrial fibrillation (AF) in the Tunisian population. MATERIALS AND METHODS: The study population included 120 patients with AF and 123 age-matched controls. Genotyping of the I/D polymorphism in the ACE gene and the -344C/T polymorphism in the CYP11B2 gene was performed by polymerase chain reaction (PCR) and PCR-RFLP methods, respectively. RESULTS: The genotype distribution of the ACE I/D and CYP11B2-344C/T polymorphisms was significantly different between AF patients and control participants (p < 0.01 and p < 0.006 respectively). In addition, ACE I/D increased the risk of AF significantly by 3.41-fold for the DD genotype (OR = 3.41; 95% CI [1.39-8.34]; p < 0.007), and after adjusting for confounding factors (age, diabetes, hypertension, and dyslipidemia), the risk was higher (OR = 5.71; 95% CI [1.48-21.98]; p < 0.01). Likewise, the CYP11B2-344C/T polymorphism increased the incidence of AF for the TT genotype (OR = 3.66; 95% CI [1.62-8.27]; p < 0.002) and the CT genotype (OR = 2.68; 95% CI [1.22-5.86]; p < 0.01). After adjusting for confounding factors (age, diabetes, hypertension and dyslipidemia), the risk remained higher for the TT genotype (OR = 3.58; 95% CI [1.08-11.77]; p < 0.03). Furthermore, the haplotype-based association of the ACE I/D and CYP11B2-344C/T polymorphisms showed that the D-T haplotype increased the risk for AF. CONCLUSION: Our study suggests a significant association of the ACE (I/D) and CYP11B2-344C/T polymorphisms with AF in the Tunisian population.

Association of BglII Polymorphism in ITGA2 and (894G/T and -786T/C) Polymorphisms in eNOS Gene With Stroke Susceptibility in Tunisian Patients α2 Gene Polymorphism in α2ß1 Integrin and eNOS Gene Variants and Stroke.

BACKGROUND: This study investigated the association of BglII polymorphism in α2ß1 integrin gene (ITGA2) and eNOS (894G/T and -786T/C) polymorphisms with ischemic stroke (IS) in Tunisian patients. METHODS: The study comprised 210 patients with IS and 208 controls. The genotypes of the BglII polymorphism in ITGA2 and eNOS (894G/T and -786T/C) polymorphisms were determined using the PCR-RFLP. The χ2 test was used and the genotype data comparison included heterozygous groups. Haplotype estimation and multiple logistic regression analysis were performed to analyze the significance of polymorphisms. RESULTS: The genotype distribution of the BglII polymorphism was significantly different between cases and controls (p < 0.004). This polymorphism was associated with the risk of IS (OR = 3.38, p < 0.001) for the BglII(+/+) genotype. Likewise, the genotype distributions of eNOS (894G/T and -786T/C) polymorphisms were significantly different between the two groups (p < 0.005 and p < 0.01, respectively). The 894G/T polymorphism increased the risk of IS for the TT genotype (OR = 2.23, p < 0.008) and the GT genotype (OR = 1.74, p < 0.009). In addition, the -786T/C variant in the eNOS gene was a risk factor for IS for CC homozygous (OR = 2.52, p < 0.005). T-C Haplotype (OR = 3.06) from combination of the eNOS (894G/T and -786T/C) and T-C-BglII(+) haplotype (OR = 2.76) from combination of eNOS and ITGA2 polymorphisms represented high risks for IS. CONCLUSIONS: This study suggests that the BglII variant in ITGA2 is associated with IS susceptibility. Furthermore, the 894G/T and -786T/C polymorphisms in the eNOS gene may be considered as genetic risk factors for IS in the Tunisian population.

Impaired nitric oxide production in patients with primary open-angle glaucoma.

BACKGROUND: Glaucoma is an optic neuropathy induced by many factors. Vascular dysfunction is involved in the mechanism underlying glaucoma. AIM: To determine the involvement of nitric oxide (NO), which is implicated in the regulation of ocular blood flow, in primary open angle glaucoma (POAG). Furthermore, lactate and uric acid (UA) levels were investigated. METHODS: Concentrations of NO, UA and lactate in plasma and aqueous humor (AH) were measured in 214 Tunisian patients (100 patients with POAG and 114 subjects with cataract as control group). NO metabolites, nitrate and nitrite (NOx) production were determined using the Griess reaction. UA and lactate concentrations were measured using enzymatic- colorimetric methods. RESULTS: NOx concentrations in patients with POAG were significantly lower compared to cataract group in plasma (5.23±1.55 µmol/L vs 18.35±6.87 µmol/L, p=0.01) and AH (20.54±7.41 µmol/L vs 45.25±10.92 µmol/L, p=0.02). Plasma and AH levels of lactate and UA were significantly higher in glaucoma patients than in control subjects. CONCLUSIONS: In the present study, decreased NO and increased UA and lactate levels were found in the AH and plasma of POAG patients compared to control subjects. These data suggest a possible involvement of these factors in glaucoma.

The Role of Genetic Variants (rs869109213 and rs2070744) Of the eNOS Gene and BglII in the α2 Subunit of the α2ß1 Integrin Gene in Diabetic Retinopathy in a Tunisian Population.

Purpose: In this study, we investigated the association of two polymorphisms (rs869109213 and rs2070744) in the eNOS gene and one polymorphism BglII in the α2ß1 integrin gene (ITGA2) with the risk of diabetic retinopathy (DR) in a Tunisian population. Methods: The study investigated of 110 type 2 diabetes mellitus (T2DM) and 127 DR patients. The genotypes of the eNOS 4b/4a (rs869109213) and -786T/C (rs2070744) polymorphisms and of the BglII polymorphism of ITGA2 were studied using the PCR or PCR-RFLP method. Results: The genotype distributions of the two polymorphisms in eNOS 4b4a and eNOS (-786T/C) were significantly different between T2DM and DR patients (p < .004 and p = .033, respectively). These polymorphisms were associated with the risk of DR (OR = 2.65, 95%CI [1.45-4.84], p = .002) for the eNOS 4b4a genotype and (OR = 2.43, 95%CI [1.06 - 5.56], p = .036) for the CC genotype of the eNOS gene (-786T/C). Similarly, the genotype distribution of the BglII polymorphism was significantly different between the two groups studied (p = .037). This polymorphism was associated with an increased risk of DR (OR = 4.03, 95% CI [1.17 - 7.85], p = .022) for BglII(+/+). Conclusion: The present study suggests that the polymorphisms 4b4a and -786T/C in the eNOS gene might be associated with DR. In addition, the BglII polymorphism in the ITGA2 gene was a risk factor for DR.

Association of MTHFR C677T, MTHFR A1298C, and MTRR A66G Polymorphisms with Neural Tube Defects in Tunisian Parents.

OBJECTIVE: This study aims to investigate the association of 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and methionine synthase reductase (MTRR A66G) gene polymorphisms with neural tube defects (NTDs) in a Tunisian population. METHODS: Genotyping was performed by polymerase chain reaction with restriction fragment length polymorphisms (PCR-RFLPs) using the restriction enzymes. Allele and genotype frequencies were compared between mothers and fathers of fetuses with NTDs with matched controls based on an association analysis using SPSS software. RESULTS: MTHFR (C677T, A1298C) and MTRR A66G polymorphisms were found to be protector factors for NTD fetuses in the mother group. In addition, a combination of the three wild-type alleles C677/A1298/A66 has increased four-fold the incidence of NTDs (p = 0.004, OR = 3.96, 95% CI: 1.53-10.23). In the father group, MTHFR C677T was a risk factor for NTDs. However, no association was found between MTHFR A1298C, MTRR A66G, and the occurrence of this anomaly. The analysis of MTHFR C677T and MTRR A66G polymorphisms has demonstrated a significant difference in vitamin B12 levels between recessive and dominant genotypes in case mothers (p < 0.05). CONCLUSION: Additional studies are required to better understand the roles of parental gene polymorphisms related to folate-homocysteine metabolism in the pathogenesis of NTD.

The A445C Variant in Apelin Receptor and Diabetic Retinopathy in Tunisian Patients.

BACKGROUND: Apelin and apelin receptor (APLN/APLNR) are involved in the retinal neovascularization of diabetic retinopathy (DR). METHODS: This study investigated the impact of the APLNR A445C variant on the risk of DR in a sample of the Tunisian population (100 patients with DR and 105 healthy controls) using PCR-RFLP. RESULTS: The genotype frequencies of the APLNR A445C variant were not significantly different between the patient and control groups. The genotype was not associated with DR (OR = 1.49; 95% CI [0.49 - 4.48], p = 0.47 for the AC heterozygous genotype and OR = 1.57; 95% CI [0.43 - 5.71], p = 0.49 for the CC homozygous genotype). Furthermore, the clinical and biochemical parameters according to the APLNR A445C genotypes revealed that only total cholesterol (TC) was significantly higher in the DR group with the CC genotype compared to the AA genotype (p < 0.02). CONCLUSIONS: The APLNR A445C polymorphism was not associated with DR in a sample of the Tunisian population, but the CC genotype carrier patients with DR had a high TC concentration.

Alpha Adducin G460T Variant is a Risk Factor for Hypertension in Tunisian Population.

BACKGROUND: Adducin is a membrane cytoskeletal protein, consisting of three subunits: α, ß, and γ subunits encoded by three different genes (ADD1, ADD2, ADD3). A specific mutation G460T of the α-adducin gene (ADD1) is associated with high renal tubular sodium reabsorption. This mutation is associated with salt sensitivity and may influence the risk of hypertension. In this study, we investigated the relationship between the G460T polymorphism of the ADD1 and essential hypertension (EH) in the Tunisian population. METHODS: The case-controlled study included 280 patients with hypertension and 257 healthy controls. The G460T polymorphism of ADD1 was determined by polymerase chain reaction-restriction fragment length polymorphism analysis method. RESULTS: In the whole population, the genotypic frequencies of the a-adducin G460T polymorphism in hypertensive and control groups (GG, GT, TT) were 78.6%, 17.5%, 3.9% and 87.5%, 11.29%, 1.16%, respectively (χ2 = 9.13, p < 0.01). The genotype was associated with hypertension, OR = 1.79, 95% CI (1.04 - 3.41), p < 0.03 for GT heterozygous and OR = 1.93, 95% CI (1.39 - 2.22), p < 0.03 for TT homozygous. Moreover, when we stratified the population according to gender, the genotypic frequencies were significantly associated with G460T polymorphism in men (p < 0.01) and in women (p < 0.05). Furthermore, no relationship was found between clinical characteristics and ADD1 G460T genotypes. CONCLUSIONS: The present study shows that the a-adducin G460T polymorphism is associated with EH. Our results suggest that this variant can be considered a genetic risk factor for hypertension in the Tunisian population.