Association of angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensinogen (AGT M235T) polymorphisms with the risk of obesity in a Tunisian population

Objective: This study aims to determine whether genetic variants in ACE I/D and AGT M235T are associated with overweight-obesity and body mass index (BMI) in a Tunisian population. Methods: We designed an age- and sex-matched case-control study. The height and weight were measured and BMI was calculated. A total of 259 overweight-obese patients and 369 healthy controls were genotyped for the ACE I/D and AGT M235T genes using polymerase chain reaction and restriction fragment length polymorphism. Results: ACE I/D and AGT M235T genes were associated with BMI, waist circumference and overweight-obesity (p⩽0.001). In an additive model, the I and the M alleles in ACE and AGT variants, respectively, were associated with a lower BMI: -1.45 and -2.29 units, respectively. ACE I/D genotypes were associated with dyslipidemia; AGT M235T genotypes with dyslipidemia and total cholesterol. Conclusion: These data suggest that variations in ACE I/D and AGT M235T affect the risk of overweight-obesity, BMI and dyslipidemia, and could point to a key molecular pathway of metabolic syndrome and its related comorbidities

Relevance of oxidative stress biomarkers, hemoglobin A1c, troponin-I, and angiotensin-converting enzyme metabolism to blood pressure in acute myocardial infarction: a case-control study

ABSTRACTThe aim was to investigate this relationship by calculating 1) the correlation between peak troponin-C (peak-cTnI), levels of oxidative stress biomarkers, including lipid peroxidation products (malondialdehyde (MDA), conjugated dienes (CD)), and antioxidant enzyme activity (glutathione peroxidase (GPx)), and HbA1c and 2) the correlation between HbA1c and serum angiotensin-converting enzyme (ACE) activity, and its impact on the rate pressure product (RPP) in acute myocardial infarction (AMI). A case-control study was performed in 306 AMI patients having undergone coronary angiography and on 410 controls. GPx activity was reduced in association with increased MDA and CD in patients. Peak-cTnI was positively correlated with HbA1c, MDA, and CD levels. Serum ACE activity was negatively correlated with GPx. HbA1c was positively correlated with ACE activity and RPP. Linear regression analysis showed that peak-cTnI, ACE activity and HbA1c are significant predictors of AMI. Elevated HbA1c and peak-cTnI levels are associated with RPP elevation causing AMI. In conclusions, patients with elevated HbA1c, elevated ACE activity and cTnI are at increased risk of AMI with increasing RPP. Patients at risk of AMI can be identified at an early stage if the biomarkers HbA1c, ACE activity, and cTnI are measured and preventive measures are taken in a targeted manner

Association between genetic variants in FADS1-FADS2 and ELOVL2 and obesity, lipid traits, and fatty acids in Tunisian population

The aim of this study was to determine whether genetic variants in FADS1/FADS2 and ELOVL2 are associated with overweight-obesity and body mass index (BMI) and to assess the association between these genetic variants and lipid profile and fatty acid levels. A total of 259 overweight-obese patients were compared to 369 healthy controls. FADS1, FADS2, and ELOVL2 genes were associated with BMI and overweight-obesity (P ≤ .001). In an additive model, the C allele in each of these variants was associated with a lower BMI: -1.18, -0.90, and -1.23 units, respectively. Higher amounts of total cholesterol, low-density lipoprotein cholesterol, total saturated fatty acids (lauric [12:0], myristic [C14:0], palmitic [C16:0], stearic [C18:0], arachidic [20:0], lignoceric [24:0]), monounsaturated fatty acids (myristoleic [C14:1], erucic [C22:1 n-9]), and polyunsaturated fatty acids (α-linolenic [ALA, 18:3 n-3], docosahexaenoic [DHA, C22:6 n-3], eicosapentaenoic acid [EPA, C20:5n-3], arachidonic acid [AA, 20:4n-6], and conjugated linolenic acids [CLA1 and CLA2]) were shown in patients. A significant increase in D6D activities presented by 20:4n-6/18:2n-6 and 18:3n-6/18:2n-6, Δ9 desaturase (D9D) activity, estimated by the ratio 18:1n-9/18:0 and elongase activities (AE), and estimated by the ratio of docosatetraenoic/AA and DPA/EPA in patients. The C minor allele of FADS1 had significantly lower DHA. A significant decrease in stearic acid, EPA, and AE activity (docosatetraenoic/AA) was revealed in patients with the minor allele carriers of FADS2. The C minor allele of ELOVL2 had significantly lower ALA, EPA, DPA, and D6D activity (C20:4 n-6/C18:2n-6). These data suggest that variations in FADS1, FADS2, and ELOVL2 affect the risk of overweight-obesity and the level of circulating fatty acids and could point to a key molecular pathway of metabolic syndrome and its related comorbidities

Nigella and milk thistle seed oils: potential cytoprotective effects against 7β-hydroxycholesterol-induced toxicity on SH-SY5Y cells

Oxysterols are assumed to be the driving force behind numerous neurodegenerative diseases. In this work, we aimed to study the ability of 7β-hydroxycholesterol (7β-OHC) to trigger oxidative stress and cell death in human neuroblastoma cells (SH-SY5Y) then the capacity of Nigella sativa and Milk thistle seed oils (NSO and MTSO, respectively) to oppose 7β-OHC-induced side effects. The impact of 7β-OHC, associated or not with NSO or MTSO, was studied on different criteria: cell viability; redox status, and apoptosis. Oxidative stress was assessed through the intracellular reactive oxygen species (ROS) production, levels of enzymatic and non-enzymatic antioxidants, lipid, and protein oxidation products. Our results indicate that 7β-OHC (40 µg/mL) exhibit pr-oxidative and pro-apoptotic activities shown by a decrease of the antioxidant enzymatic activities and an increase of ROS production, lipid, and protein oxidation end products as well as nitrotyrosine formation and caspase 3 activation. However, under the pre-treatment with NSO, and especially with MTSO (100 µg/mL), a marked attenuation of oxidative damages was observed. Our study suggests harmful effects of 7β-OHC consisting of pro-oxidative, anti-proliferative, and pro-apoptotic activities that may contribute to neurodegeneration. NSO and especially MTSO showed potential cytoprotection against the cytotoxicity of 7β-OHC.This study was supported by the Ministry of Higher Education and Scientific Research (MHESR), Tunisia. This work was also supported by the Spanish Ministry of Science and Innovation and FEDER Funds through grants SAF2017-83372-R (FJM) and through the “María de Maeztu” Program for Units of Excellence in R&D from Spain (award CEX2018-000792-M)