Low HDL-C/ApoA-I index is associated with cardiometabolic risk factors and coronary artery calcium: a sub-analysis of the genetics of atherosclerotic disease (GEA) study.

BACKGROUND: The high-density lipoprotein cholesterol to apolipoprotein A-I index (HDL-C/ApoA-I) may be practical and useful in clinical practice as a marker of atherosclerosis. This study aimed to investigate the association between the HDL-C/ApoA-I index with cardiometabolic risk factors and subclinical atherosclerosis. METHODS: In this cross-sectional sub-analysis of the GEA study, 1,363 individuals, women (51.3%) and men (48.7%) between 20 and 75 years old, without coronary heart disease or diabetes mellitus were included. We defined an adverse cardiometabolic profile as excess adipose tissue metrics, non-alcoholic liver fat measured by non-contrasted tomography, metabolic syndrome, dyslipidemias, and insulin resistance. The population was stratified by quartiles of the HDL-C/Apo-AI index, and its dose-relationship associations were analysed using Tobit regression, binomial, and multinomial logistic regression analysis. RESULTS: Body mass index, visceral and pericardial fat, metabolic syndrome, fatty liver, high blood pressure, and CAC were inversely associated with the HDL-C/ApoA-I index. The CAC > 0 prevalence was higher in quartile 1 (29.2%) than in the last quartile (22%) of HDL-C/ApoA-I index (p = 0.035). The probability of having CAC > 0 was higher when the HDL-C/ApoA-I index was less than 0.28 (p < 0.001). This association was independent of classical coronary risk factors, visceral and pericardial fat measurements. CONCLUSION: The HDL-C/ApoA-I index is inversely associated with an adverse cardiometabolic profile and CAC score, making it a potentially useful and practical biomarker of coronary atherosclerosis. Overall, these findings suggest that the HDL-C/ApoA-I index could be useful for evaluating the probability of having higher cardiometabolic risk factors and subclinical atherosclerosis in adults without CAD.

MCP-1 rs1024611 Polymorphism, MCP-1 Concentrations, and Premature Coronary Artery Disease: Results of the Genetics of Atherosclerotic Disease (GEA) Mexican Study.

Monocyte chemoattractant protein-1 (MCP-1) participates in the initiation and progression of atherosclerosis. In vitro studies have reported that the MCP-1 rs1024611 polymorphism is associated with increased MCP-1 concentrations. The study aimed to define whether MCP-1 concentrations are associated with premature coronary artery disease (pCAD) and to establish whether variations in the rs1024611 polymorphism increase MCP-1 concentrations. MCP-1 rs1024611 polymorphism was determined in 972 pCAD patients and 1070 control individuals by real-time PCR. MCP-1 concentrations were determined by the Bio-Plex system. In the total population, men had higher MCP-1 concentrations when compared to women (p < 0.001). When stratified by rs1024611 genotypes, higher MCP-1 concentrations were observed in AA individuals compared to GG subjects (p = 0.023). When performing the analysis considering sex, the differences remained significant in women (AA vs. GG, p = 0.028 and GA vs. GG, p = 0.008). MCP-1 concentrations were similar in pCAD patients and controls (p = 0.782). However, the independent analysis of the studied groups showed that in patients with the AA genotype, MCP-1 concentrations were significantly higher when compared to patients with the GG genotype (p = 0.009). Considering that the AA genotype increases MCP-1 concentration, we evaluated whether, in AA genotype carriers, MCP-1 concentrations were associated with pCAD. The results showed that for every ten pg/mL increase in MCP-1 concentration, the risk of presenting pCAD increases by 2.7% in AA genotype individuals. Individuals with the MCP-1 rs1024611 AA genotype present an increase in MCP-1 concentration. In those individuals, increased MCP-1 concentrations increase the risk of presented pCAD.

Impact of Lipids and Vascular Damage on Early Atherosclerosis in Adolescents with Parental Premature Coronary Artery Disease.

AIM: To assess the relationship of cardiovascular risk factors (CRFs) with carotid intima media thickness (IMT) in adolescents with a parental history of premature coronary artery disease (PCAD). METHODS: This cross-sectional study included 50 healthy adolescents, aged 14-18 years, both sexes, with a parental history of PCAD, that were compared to 50 controls without this history. Questionnaires regarding information of CRFs were applied. Blood chemistry analyses, included lipid profile, lipoprotein (a), low density lipoprotein (LDL) susceptibility to oxidation, and inflammatory cytokine levels. The IMT was evaluated by ultrasound. RESULTS: The mean age of all participants was 15.9 years. Anthropometric measurements, blood pressure, and lipid profile were similar in both groups. However, the parental history of PCAD group exhibited lower high density lipoprotein cholesterol concentrations, shorter LDL particle oxidation time, and higher lipoprotein (a) levels compared to the control group. IMT was significantly higher in adolescents with a parental history of PCAD compared to controls, (0.53 ± 0.04 mm vs 0.47 ± 0.02 mm, p = 0.001). Among adolescents with a parental history of PCAD, those with ≥ 3 CRFs had significantly higher IMT values (0.56 mm) than those with < 3 CRFs (0.52 mm) and controls (0.48 mm). Multivariable analyses identified that systolic blood pressure and parental history of PCAD explained 26.8% and 16.1% of the variation in IMT. Furthermore, body mass index, LDL-C, ApoB-100, triglycerides and lipoprotein (a) interact with blood pressure levels to explain the IMT values. CONCLUSION: Adolescents with a parental history of PCAD had higher IMT values than the control group, primary explained by systolic blood pressure and the parental inheritance. Adolescents with parental history of PCAD and ≥ 3 CRFs exhibited the highest IMT values. Notably, lipids and systolic blood pressure jointly contribute to explain IMT in these adolescents.

Smooth Muscle Cells from a Rat Model of Obesity and Hyperleptinemia Are Partially Resistant to Leptin-Induced Reactive Oxygen Species Generation.

The aim of this study was to evaluate the effect of leptin on reactive oxygen species' (ROS) generation of smooth muscle cells (SMCs) from a rat model of obesity and hyperleptinemia. Obesity and hyperleptinemia were induced in rats by a sucrose-based diet for 24 weeks. ROS generation was detected by using dichloro-dihydrofluorescein (DCF), a fluorescent ROS probe in primary SMCs culture. An increase in plasma leptin and oxidative stress markers was observed in sucrose-fed (SF) rats. At baseline SMCs from SF rats showed a more than twofold increase in fluorescence intensity (FI) compared to that obtained in control (C) cells. When the C cells were treated with 20 ng leptin, the FI increased by about 250%, whereas the leptin-induced FI in the SF cells increased only by 28%. In addition, sucrose feeding increased the levels of p22phox and gp91phox, subunits of Nox as an O2•- source in SMCs. Treatment of cells with leptin significantly increased p22phox and gp91phox levels in C cells and did not affect SF cells. Regarding STAT3 phosphorylation and the content of PTP1B and SOCS3 as protein markers of leptin resistance, they were found to be significantly increased in SF cells. These results suggest that SF aortic SMCs are partially resistant to leptin-induced ROS generation.

Helicobacter pylori infection and DNMT3a polymorphism are associated with the presence of premature coronary artery disease and subclinical atherosclerosis. Data from the GEA Mexican Study.

BACKGROUND: The association between H. pylori infection and coronary artery disease (CAD) is well-known. Alterations in DNA methylation in CAD have been reported, which can be induced by H. pylori through the DNA demethylases (DNMTs). The objective was to analyze the association and interaction of H. pylori infection and DMNT3a gene polymorphisms with premature CAD (pCAD) and subclinical atherosclerosis (SA). METHODS: The study included 561 patients with pCAD, 318 subjects with SA, and 599 healthy controls. Antibodies against H. pylori and DNMT3a rs13420827, rs752208, and rs1550117 polymorphisms were determined. RESULTS: The pCAD group presented the highest seroprevalence of H. pylori infection (87.7%) compared to the SA (74.5%, p = 1 × 10-6) and the control group (63.1%, p = 7 × 10-23). A significant association was observed between H. pylori infection and pCAD (OR = 2.729, p = 1.0 × 10-6). The rs13420827 polymorphism was associated with a high risk of H. pylori infection in the whole population (padditive = 0.009, pdominant = 0.018, and pcodominant2 = 0.013) and in individuals with SA (padditive = 0.003, pdominant = 0.020, precessive = 0.013, and pcodominant2 = 0.005). The coexistence of H. pylori infection and the rs13420827GG genotype increases the risk of pCAD (pinteraction = 1.1 × 10-5). CONCLUSIONS: According to the model adjusted for more confounding variables, H. pylori infection was associated with almost three times the risk of developing pCAD. The rs13420827G allele was associated with an increased risk of H. pylori infection in the whole population and in individuals with SA. Individuals in whom H. pylori infection and the rs13420827GG genotype coexist are at increased risk of pCAD.

Síndrome metabólico, lipoproteína(a) y aterosclerosis subclínica en población mexicana / Metabolic syndrome, lipoprotein(a) and subclinical atherosclerosis in Mexican population

Resumen Objetivo: Investigar la asociación del síndrome metabólico y la lipoproteína(a) [Lp(a)] con el riesgo de aterosclerosis subclínica en adultos mexicanos. Método: En 953 mujeres y hombres se evaluaron datos clínicos, bioquímicos y tomográficos de grasa abdominal visceral, subcutánea, hepática y calcio arterial coronario. La Lp(a) se determinó mediante nefelometría y el síndrome metabólico se diagnosticó con los criterios del Adult Treatment Panel III. La asociación independiente de estas variables con el calcio arterial coronario se obtuvo con análisis de regresión logística multivariada. Resultados: La edad, el peso, el índice de masa corporal, la presión arterial sistólica y diastólica, los volúmenes de grasa abdominal, los lípidos, la glucosa, la insulina y el índice de resistencia a insulina fueron significativamente mayores en los sujetos con síndrome metabólico, mientras que la mediana de Lp(a) fue más baja en comparación con los sujetos sin el síndrome (3.7 [rango intercuartílico (RIC): 2.3-9.2 vs. 5.9 [RIC: 2.5-13.1) mg/dl; p < 0.01). El número de componentes y el síndrome metabólico se asociaron inversamente con la Lp(a) elevada (> 30 mg/dl). La presencia de síndrome metabólico se asoció con un riesgo de calcio arterial coronario > 0 (odds ratio [OR]: 2.19; intervalo de confianza del 95% [IC95%]: 1.64-2.94; p < 0.001), independientemente de la Lp(a) elevada. La glucemia > 100 mg/dl (OR: 2.42; IC95%: 1.7-3.4; p < 0.0001) y la presión arterial elevada (OR: 2.14; IC95%: 1.5-3.1; p > 0.0001) se asociaron con calcio arterial coronario > 0. Conclusiones: En población mexicana existe una asociación inversa entre la concentración de Lp(a) y el síndrome metabólico. Este y sus componentes se asociaron positivamente con aterosclerosis subclínica. La elevada prevalencia de obesidad, diabetes, hipertensión arterial, triglicéridos elevados y concentración de colesterol unido a lipoproteínas de alta densidad que caracterizan a la población mexicana pudieran explicar las diferencias con otras poblaciones.

Abstract Objective: To assess the relationship of metabolic syndrome (MetS) and Lp(a) with subclinical atherosclerosis (CAC) in Mexican adults. Method: Clinical, biochemical and tomographic data of visceral, subcutaneous, hepatic abdominal fat and CAC were evaluated in 953 women and men. Lp(a) was determined by nephelometry and MetS was diagnosed according to ATP III criteria. Multivariate logistic regression analysis was performed to determine the independent association of these variables with CAC. Results: Age, weight, body mass index, systolic and diastolic blood pressure, volumes of visceral, subcutaneous and hepatic abdominal fat, lipids, glucose, insulin and HOMA-RI were significantly higher in subjects with MetS. The median Lp(a) was lower in subjects with MetS compared to subjects without MetS (3.7 [IR: 2.3-9.2 vs. 5.9 [IR: 2.5-13.1) mg/dL; p < 0.01). The number of components and the MetS were inversely associated with the elevated Lp(a) (> 30 mg / dL). The presence of MetS was associated with a CAC risk >0 (OR: 2.19, [95% CI (1.64-2.94)]; p < 0.001), independently of elevated Lp(a). The components of MetS that were independently associated with the presence of CAC > 0 UA were glycaemia > 100 mg/dL (OR 2.42, [95% CI (1.7-3.4)]; p < 0.0001) and high blood pressure (OR 2.14 [95% CI (1.5-3.1)]; p < 0.0001). Conclusions: In Mexican population there is an inverse association between Lp(a) levels and MetS. The MetS and its components were associated with subclinical atherosclerosis. The high prevalence of obesity, diabetes, high blood pressure high triglycerides and low HDL-C, characteristics of Mexican population could explain the differences with other populations.

High fructose exposure modifies the amount of adipocyte-secreted microRNAs into extracellular vesicles in supernatants and plasma.

BACKGROUND: High fructose exposure induces metabolic and endocrine responses in adipose tissue. Recent evidence suggests that microRNAs in extracellular vesicles are endocrine signals secreted by adipocytes. Fructose exposure on the secretion of microRNA by tissues and cells is poorly studied. Thus, the aim of this study was to evaluate the effect of fructose exposure on the secretion of selected microRNAs in extracellular vesicles from 3T3-L1 cells and plasma from Wistar rats. METHODS: 3T3-L1 cells were exposed to 550 µM of fructose or standard media for four days, microRNAs levels were determined in extracellular vesicles of supernatants and cells by RT-qPCR. Wistar rats were exposed to either 20% fructose drink or tap water for eight weeks, microRNAs levels were determined in extracellular vesicles of plasma and adipose tissue by RT-qPCR. RESULTS: This study showed that fructose exposure increased the total number of extracellular vesicles released by 3T3-L1 cells (p = 0.0001). The levels of miR-143-5p were increased in extracellular vesicles of 3T3-L1 cells exposed to fructose (p = 0.0286), whereas miR-223-3p levels were reduced (p = 0.0286). Moreover, in plasma-derived extracellular vesicles, miR-143-5p was higher in fructose-fed rats (p = 0.001), whereas miR-223-3p (p = 0.022), miR-342-3p (p = 0.0011), miR-140-5p (p = 0.0129) and miR-146b-5p (p = 0.0245) were lower. CONCLUSION: Fructose exposure modifies the levels of microRNAs in extracellular vesicles in vitro and in vivo. In particular, fructose exposure increases miR-143-5p, while decreases miR-223-3p and miR-342-3p.

Interferon Regulatory Factor 5 (IRF5) Gene Haplotypes Are Associated with Premature Coronary Artery Disease. Association of the IRF5 Polymorphisms with Cardiometabolic Parameters. The Genetics of Atherosclerotic Disease (GEA) Mexican Study.

Interferon regulatory factor 5 (IRF5) has an important role in the inflammatory process, a fundamental component of coronary artery disease (CAD). Thus, the objective of this study was to evaluate the association of IRF5 polymorphisms with the development of premature CAD (pCAD) and cardiometabolic parameters. IRF5 polymorphisms (rs1874330, rs3778754, rs3757386, rs3757385, rs3807134, rs3807135, and rs6968563) were determined in 1116 pCAD patients and 1003 controls. Polymorphism distribution was similar in patients and controls; however, the haplotype analysis showed five haplotypes with a different distribution. TGCGTCT (OR (odds ratio) = 1.248, p = 0005) and TCTGCCT (OR = 10.73, p < 0.0001) were associated with a high risk, whereas TCCGTCT (OR = 0.155, p < 0.0001), CGCTTTT (OR = 0.108, p < 0.0001), and TCCGCCT (OR = 0.014, p < 0.0001) were associated with a low risk of pCAD. Associations with aspartate aminotransferase, hypertriglyceridemia, magnesium deficiency, triglycerides/HDL-C index, LDL-C, and adiponectin levels were observed in pCAD patients. In controls, associations with hypoalphalipoproteinemia, non-HDL-C, apolipoprotein B, hyperuricemia, TNF-α, IL-6, IL-15, valvular calcification, and subclinical hypothyroidism were observed. In summary, five haplotypes were associated with pCAD, two with high risk and three with low risk. Some IRF5 polymorphisms were associated with cardiometabolic parameters in pCAD patients and control.

Metabolic syndrome, lipoprotein(a) and subclinical atherosclerosis in Mexican population / Síndrome metabólico, lipoproteína(a) y aterosclerosis subclínica en población mexicana

Objective: To assess the relationship of metabolic syndrome (MetS) and Lp(a) with subclinical atherosclerosis (CAC) in Mexican adults. Method: Clinical, biochemical and tomographic data of visceral, subcutaneous, hepatic abdominal fat and CAC were evaluated in 953 women and men. Lp(a) was determined by nephelometry and MetS was diagnosed according to ATP III criteria. Multivariate logistic regression analysis was performed to determine the independent association of these variables with CAC. Results: Age, weight, body mass index, systolic and diastolic blood pressure, volumes of visceral, subcutaneous and hepatic abdominal fat, lipids, glucose, insulin and HOMA-RI were significantly higher in subjects with MetS. The median Lp(a) was lower in subjects with MetS compared to subjects without MetS (3.7 [IR: 2.3-9.2 vs. 5.9 [IR: 2.5-13.1) mg/dL; p < 0.01). The number of components and the MetS were inversely associated with the elevated Lp(a) (> 30 mg / dL). The presence of MetS was associated with a CAC risk >0 (OR: 2.19, [95% CI (1.64-2.94)]; p < 0.001), independently of elevated Lp(a). The components of MetS that were independently associated with the presence of CAC > 0 UA were glycaemia > 100 mg/dL (OR 2.42, [95% CI (1.7-3.4)]; p < 0.0001) and high blood pressure (OR 2.14 [95% CI (1.5-3.1)]; p < 0.0001). Conclusions: In Mexican population there is an inverse association between Lp(a) levels and MetS. The MetS and its components were associated with subclinical atherosclerosis. The high prevalence of obesity, diabetes, high blood pressure high triglycerides and low HDL-C, characteristics of Mexican population could explain the differences with other populations.

Objetivo: Investigar la asociación del síndrome metabólico y la lipoproteína(a) [Lp(a)] con el riesgo de aterosclerosis subclínica en adultos mexicanos. Método: En 953 mujeres y hombres se evaluaron datos clínicos, bioquímicos y tomográficos de grasa abdominal visceral, subcutánea, hepática y calcio arterial coronario. La Lp(a) se determinó mediante nefelometría y el síndrome metabólico se diagnosticó con los criterios del Adult Treatment Panel III. La asociación independiente de estas variables con el calcio arterial coronario se obtuvo con análisis de regresión logística multivariada. Resultados: La edad, el peso, el índice de masa corporal, la presión arterial sistólica y diastólica, los volúmenes de grasa abdominal, los lípidos, la glucosa, la insulina y el índice de resistencia a insulina fueron significativamente mayores en los sujetos con síndrome metabólico, mientras que la mediana de Lp(a) fue más baja en comparación con los sujetos sin el síndrome (3.7 [rango intercuartílico (RIC): 2.3-9.2 vs. 5.9 [RIC: 2.5-13.1) mg/dl; p < 0.01). El número de componentes y el síndrome metabólico se asociaron inversamente con la Lp(a) elevada (> 30 mg/dl). La presencia de síndrome metabólico se asoció con un riesgo de calcio arterial coronario > 0 (odds ratio [OR]: 2.19; intervalo de confianza del 95% [IC95%]: 1.64-2.94; p < 0.001), independientemente de la Lp(a) elevada. La glucemia > 100 mg/dl (OR: 2.42; IC95%: 1.7-3.4; p < 0.0001) y la presión arterial elevada (OR: 2.14; IC95%: 1.5-3.1; p > 0.0001) se asociaron con calcio arterial coronario > 0. Conclusiones: En población mexicana existe una asociación inversa entre la concentración de Lp(a) y el síndrome metabólico. Este y sus componentes se asociaron positivamente con aterosclerosis subclínica. La elevada prevalencia de obesidad, diabetes, hipertensión arterial, triglicéridos elevados y concentración de colesterol unido a lipoproteínas de alta densidad que caracterizan a la población mexicana pudieran explicar las diferencias con otras poblaciones.

Epstein-Barr virus-induced gene 3 (EBI3) single nucleotide polymorphisms and their association with central obesity and risk factors for cardiovascular disease: The GEA study.

Obesity, a chronic low-grade inflammation metabolic abnormality, is related to high proinflammatory cytokines concentrations. Epstein-Barr virus-induced gene 3 (EBI3) encodes for the EBI3 beta subunit that constitutes interleukin (IL) 27 and 35. Our objective was to assess the association of three EBI3 single nucleotide polymorphisms (SNPs) with the presence of central obesity in a group of Mexican subjects. The rs428253, rs4740, and rs4905 EBI3 SNPs were genotyped in 1323 individuals (1092 central obese and 231 non-central obese). We also analyzed IL-6, IL-27, and IL-35 concentrations. Under different models, the rs4740 (OR = 0.384, Precessive = 0.010; OR = 0.404, Pcodominant 2 = 0.019) and rs4905 (OR = 0.380, Precessive = 0.009; OR = 0.404, Pcodominant 2 = 0.018) were related with a low risk of central obesity. In central obese subjects, the SNPs were related to lower risk of hypoalphalipoproteinemia (rs4740) and with high IL-6 concentrations (rs428253, rs4740, and rs4905), whereas in non-central obese individuals, the rs428253 was related with low risk of increased visceral abdominal fat and hypertriglyceridemia. Interleukin-6, IL-27 and IL-35 concentrations were similar in both groups and no relation was noticed with the studied genotypes. Our results suggest an association of EBI3 SNPs with a low risk of central obesity and with a few risk factors for cardiovascular disease in individuals with and without central obesity.

CORONARY ARTERY CALCIUM IS ASSOCIATED WITH LPA GENE VARIANT RS7765803-C IN MEXICAN MESTIZO POPULATION. THE GEA PROJECT.

BACKGROUND: Lipoprotein(a) [Lp(a)] levels are genetically determined; high levels are a risk factor for coronary disease, although their association with coronary artery calcium (CAC) is controversial. Objective: The objective of the study was to assess the association of LPA gene polymorphisms with CAC in a Mexican Mestizo population. METHODS: We included 1594 subjects 35-70 years old. Six polymorphisms of the LPA gene were analyzed. CAC score was determined by tomography and Lp(a) serum levels by immunonephelometry. The association of LPA polymorphism with CAC and Lp(a) was evaluated by logistic regression. RESULTS: The prevalence of Lp(a) ≥30 mg/dL was 10%, and of CAC >0 was 26.9%. Three polymorphisms were associated with high Lp(a) levels: rs10455872-G (p = 0.013), rs6907156-T (p = 0.021), and rs7765803-C (p = 0.001). Homozygotes (CC) for the rs7765803 variant compared with the G allele (CG + GG) carriers had higher Lp(a) levels (8.9 [3.3-23.9] vs. 4.9 [2.3-11.2] mg/dL; p = 0.015) and higher prevalence of CAC >0 (36.5% vs. 26.3%, p = 0.045) and were associated with CAC > 0 (odds ratio = 1.7, 95% confidence interval: 1.06-2.7; p < 0.026). The other polymorphisms were not associated with CAC. CONCLUSIONS: This is the first study to demonstrate in a Mexican Mestizo population that carriers of the rs7765803-C allele of LPA gene have 2.6 times greater risk for high Lp(a) values and 1.7 times higher risk for coronary artery disease.

Coronary artery calcium is associated with lpa gene variant RS7765803-C in Mexican mestizo population The GEA Project

ABSTRACT Background: Lipoprotein(a) [Lp(a)] levels are genetically determined; high levels are a risk factor for coronary disease, although their association with coronary artery calcium (CAC) is controversial. Objective: The objective of the study was to assess the association of LPA gene polymorphisms with CAC in a Mexican Mestizo population. Methods: We included 1594 subjects 35-70 years old. Six polymorphisms of the LPA gene were analyzed. CAC score was determined by tomography and Lp(a) serum levels by immunonephelometry. The association of LPA polymorphism with CAC and Lp(a) was evaluated by logistic regression. Results: The prevalence of Lp(a) ≥30 mg/dL was 10%, and of CAC >0 was 26.9%. Three polymorphisms were associated with high Lp(a) levels: rs10455872-G (p = 0.013), rs6907156-T (p = 0.021), and rs7765803-C (p = 0.001). Homozygotes (CC) for the rs7765803 variant compared with the G allele (CG + GG) carriers had higher Lp(a) levels (8.9 [3.3-23.9] vs. 4.9 [2.3-11.2] mg/dL; p = 0.015) and higher prevalence of CAC >0 (36.5% vs. 26.3%, p = 0.045) and were associated with CAC > 0 (odds ratio = 1.7, 95% confidence interval: 1.06-2.7; p < 0.026). The other polymorphisms were not associated with CAC. Conclusions: This is the first study to demonstrate in a Mexican Mestizo population that carriers of the rs7765803-C allele of LPA gene have 2.6 times greater risk for high Lp(a) values and 1.7 times higher risk for coronary artery disease.

THE BRANCHED-CHAIN AMINO ACID TRANSAMINASE 1 -23C/G POLYMORPHISM CONFERS PROTECTION AGAINST ACUTE CORONARY SYNDROME.

BACKGROUND: Previous studies have shown an association between polymorphisms of the BAT1-NF-κB inhibitor-like-1 (NFKBIL1)-LTA genomic region and susceptibility to myocardial infarction and acute coronary syndrome (ACS). OBJECTIVE: The objective of the study was to study the role of three polymorphisms in the BAT1, NFKBIL1, and LTA genes on the susceptibility or protection against ACS; we included a group of cases-controls from Central Mexico. METHODS: The BAT1 rs2239527C/G, NFKBIL1 rs2071592T/A, and LTA rs1800683G/A polymorphisms were genotyped using a 5' TaqMan assay in a group of 625 patients with ACS and 617 healthy controls. RESULTS: Under a recessive model, the BAT1 -23C/G (rs2239527) polymorphism showed an association with protection against ACS (odds ratio = 0.56, and p-corrected = 0.019). In contrast, the genotype and allele frequencies of the NFKBIL1 rs2071592T/A and LTA rs1800683G/A polymorphisms were similar between ACS patients and controls and no association was identified. CONCLUSION: Our data suggest an association between the BAT1 -23C/G polymorphism and protection against ACS in Mexican patients.

The branched-chain amino acid transaminase 1 -23c/g polymorphism confers protection against acute coronary syndrome

ABSTRACT Background: Previous studies have shown an association between polymorphisms of the BAT1-NF-κB inhibitor-like-1 (NFKBIL1)-LTA genomic region and susceptibility to myocardial infarction and acute coronary syndrome (ACS). Objective: The objective of the study was to study the role of three polymorphisms in the BAT1, NFKBIL1, and LTA genes on the susceptibility or protection against ACS; we included a group of cases-controls from Central Mexico. Methods: The BAT1 rs2239527C/G, NFKBIL1 rs2071592T/A, and LTA rs1800683G/A polymorphisms were genotyped using a 5' TaqMan assay in a group of 625 patients with ACS and 617 healthy controls. Results: Under a recessive model, the BAT1 -23C/G (rs2239527) polymorphism showed an association with protection against ACS (odds ratio = 0.56, and p-corrected = 0.019). In contrast, the genotype and allele frequencies of the NFKBIL1 rs2071592T/A and LTA rs1800683G/A polymorphisms were similar between ACS patients and controls and no association was identified. Conclusion: Our data suggest an association between the BAT1 -23C/G polymorphism and protection against ACS in Mexican patients.

Phenotypes and concentration of PON1 in cardiovascular disease: The role of nutrient intake.

BACKGROUND AND AIMS: Paraoxonase 1 (PON1) is considered to play a crucial role as an anti-atherosclerotic factor. The PON1 activity is affected by genetic polymorphisms, environmental factors, age, sex, lifestyle, pharmaceutical drugs, and dietary factors. The aim of this study was to evaluate the association between macro- and micronutrients as well as PON1 concentration and activities in patients with cardiovascular diseases (CVD), cardiovascular risk factors but no CVD (CRF), and in healthy controls (control group). METHODS AND RESULTS: A case-control study was carried out with 356 volunteers from the Mexican Institute of Social Security, Mexico. Clinical parameters, lipid profile, PON1 activities (AREase, LACase, CMPAase and PONase), and PON1 concentration were evaluated. There was a differential intake of macro- and micronutrients among the study groups. The intake of proteins and carbohydrates was higher in the CVD group than in the CFR and control groups (p < 0.05). AREase, LACase, and CMPAase activities and PON1 concentration were lowest in the CVD group. CONCLUSION: LACase and CMPAase activities, as well as PON1 concentration, could be included in the battery of CVD predictive biomarkers in the Mexican population.

SREBF1c and SREBF2 gene polymorphisms are associated with acute coronary syndrome and blood lipid levels in Mexican population.

AIM: It has recently been reported that the sterol regulatory element-binding transcription factors (SREBF-1c, and -2) contribute to the variation in the plasma lipids levels, which have an important role in the atherosclerotic plaque development. The aim of the present study was to evaluate whether the SREBF1c and SREBF2 gene single nucleotide polymorphisms (SNPs) are associated with plasma lipids levels and ACS susceptibility in a case-control association study. MATERIAL AND METHODS: A case-control study was carried out in 625 patients with ACS (82% men and 18% women, with a mean age of 57.97 ± 10.5 years) and 700 healthy controls (66% men and 34% women, with a mean age of 54.37 ± 7.65 years). The sample size was calculated for a statistical power of 80%. We genotyped three SREBF1c (rs2297508, rs11656665 and rs11868035) and three SREBF2 (rs2267439, rs2267443, and rs2228314) gene polymorphisms by 5' exonuclease TaqMan assays. The associations were evaluated by logistic regression under the co-dominant, dominant, recessive, over-dominant and additive inheritance models. The contribution of the genotypes on the plasma lipids levels was evaluated by Student's t-test. RESULTS: Under different models, the SREBF1c rs2297508 (OR = 1.50, pCRes = 0.03), SREBF1c rs11656665 (OR = 1.35, pCDom = 0.02 and OR = 1.26, pCAdd = 0.02) and SREBF2 rs2228314 (OR = 1.78, pCRes = 0.03, OR = 1.27, pCAdd = 0.04) SNPs were associated with higher risk of ACS. On the other hand, the SREBF1c rs11868035 SNP was associated with lower risk of ACS (OR = 0.49, pCCo-dom = 0.001, OR = 0.66, pCDom = 0.003, OR = 0.57, PRes = 0.003 and OR = 0.71, pCAdd = 0.001). There was a statistically significant association of both SREBF1c rs11656665 and rs11868035 polymorphisms with plasma triglyceride levels. CONCLUSIONS: In summary, our data suggest the association of the SREBF1c and SREBF2 SNPs with risk of developing ACS and with triglyceride levels in a Mexican population.

MRE11A Polymorphisms Are Associated With Subclinical Atherosclerosis and Cardiovascular Risk Factors. A Case-Control Study of the GEA Mexican Project.

DNA damage and subsequent repair pathways have been involved in the initiation and progression of atherosclerosis. Meiotic recombination 11 homolog A (MRE11A) gene polymorphisms have been associated with the presence of myocardial infarction. We analyzed five MRE11A gene polymorphisms in 386 individuals with subclinical atherosclerosis and 1093 healthy controls. Under different models, the rs13447720 (Odds ratio = 0.646, Padditive = 0.009; Odds ratio = 0.636, Pdominant = 0.012; Odds ratio = 0.664, Pover-dominant = 0.025; Odds ratio = 0.655, Pcodominant1 = 0.021) and rs499952 (Odds ratio = 0.807, Padditive = 0.032; Odds ratio = 0.643, Pcodominant2 = 0.034) polymorphisms were associated with a lower risk of subclinical atherosclerosis. On the other hand, the rs2155209 polymorphism was associated with a reduced risk of having a coronary artery calcification score ≥ 100 Agatston units. The rs13447720, rs499952, and rs2155209 polymorphisms, as well as the haplotypes that included the five studied polymorphisms were associated with some clinical and metabolic parameters in both subclinical atherosclerosis and healthy individuals. Our results suggest that the rs13447720 and rs499952 polymorphisms are associated with a decreased risk of developing subclinical atherosclerosis, whereas the rs2155209 is associated with a lower subclinical atherosclerosis severity (coronary artery calcification < 100 Agatston units). MRE11A polymorphisms and haplotypes were associated with clinical and metabolic parameters.

The rs2066808 Polymorphism Located Near the IL-23A Gene Is Associated with Premature Coronary Artery Disease in Mexican Population (GEA Study).

Interleukin-23 (IL-23) has been associated with atherosclerosis in both humans and animal models with contradictory results. This cytokine is conformed by an α p19 (encoded by IL-23A gene) and a ß p40 subunit (encoded by IL-12B gene). The aim of this study was to evaluate the association of two polymorphisms located within (rs11171806) or near (rs2066808) of the IL-23A gene with the presence of premature coronary artery disease (CAD) and with cardiometabolic parameters. The rs2066808 and rs11171806 polymorphisms were determined in 2249 Mexican individuals (1160 with premature CAD and 1089 healthy controls). Under recessive and codominant 2 models, adjusted by confounding variables, the rs2066808 polymorphism could increase the genetic risk of premature CAD (odds ratio [OR] = 4.567, 95% confidence interval [CI]: 1.03-20.24, Precessive = 0.046 and OR = 4.606, 95% CI: 1.039-20.43, Pcodominant2 = 0.044). The association of the polymorphisms with cardiovascular risk factors was evaluated separately in premature CAD patients and healthy controls. In patients, the rs2066808 polymorphism could decrease the genetic risk of hyperinsulinemia, insulin resistance, and hypoalphalipoproteinemia, and increase the genetic risk of hyperuricemia, whereas the rs11171806 polymorphism could decrease the genetic risk of hyperinsulinemia and insulin resistance. In healthy controls, the rs11171806 polymorphism could decrease the genetic risk of hyperinsulinemia. These findings suggest that the rs2066808 polymorphism located near the IL-23A gene could increase the genetic risk of premature CAD and both studied polymorphisms could be associated with some cardiometabolic parameters in premature CAD patients and in healthy controls.

PON1 concentration and high-density lipoprotein characteristics as cardiovascular biomarkers.

INTRODUCTION: Serum paraoxonase 1 (PON1) is now known to be related to cardiovascular diseases (CVD). The aim of this study was to determine the relationship between PON1 concentration and high-density lipoprotein (HDL) subclasses in patients with proven CVD, cardiovascular risk factors but no CVD (CRF), and in healthy controls (control group). MATERIAL AND METHODS: A case-control study was carried out with 69 volunteers from the Mexican Institute of Social Security, Mexico. Clinical parameters, lipid profile, PON1 concentration, PON1 activities (AREase and CMPAase), and HDL subclasses were evaluated. RESULTS: Patients with CVD had significantly higher glucose and lower total cholesterol than the control group had (p < 0.01). AREase activity was not different between the control (122.57 ±30.72 U/ml), CRF (115.81 ±32.81 U/ml), and CVD (109.34 ±29.60 U/ml) groups. PON1 concentration was significantly lower in CVD patients than in CRF and control patients (p < 0.001); a positive correlation was observed between AREase activity and PON1 concentration in the CVD group (Rho = 0.58; p < 0.01). Logistic regression analysis showed that the decrease in PON1 level was associated with the CVD group (RRR = 0.20; 95% CI: 0.09-0.45) but not with the CRF group (RRR = 1.29; 95% CI: 0.89-1.90). Significant differences were observed in HDL 2a and HDL 3a concentrations between the control group and CRF and CVD groups (p < 0.05), but not between the CRF and CVD groups. CONCLUSIONS: Our data suggest that PON1 status and HDL characteristics could be early biomarkers that predict the potential for developing CVD.

The rs10455872-G allele of the LPA gene is associated with high lipoprotein(a) levels and increased aortic valve calcium in a Mexican adult population.

Polymorphisms in the LPA gene have been associated with aortic valve calcification (AVC). There are wide differences in the allelic frequencies, Lp(a) levels, and the association with AVC among ethnic groups. The aim of this study was to determine the association of the LPA gene polymorphisms with Lp(a) levels and risk of developing AVC, in Mexican-Mestizos population. Six LPA polymorphisms (rs10455872, rs7765803, rs6907156, rs1321195, rs12212807 and rs6919346) were genotyped by TaqMan assays in 1,265 individuals without premature coronary artery disease. The presence of AVC was determined by computed tomography. The association of the LPA polymorphisms with AVC, Lp(a), and other cardiovascular risk factors (CVRF) was evaluated using logistic regression analysis. Compared to AA genotype, subjects with AG+GG genotypes had high prevalence of Lp(a) ≥ 30 mg/dL (7.1% vs. 23.7%, p<0.001) and AVC (19.0% vs. 29.4%, p=0.007). In a model adjusted for several CVRF, the LPA rs10455872-G allele was associated with high Lp(a) levels and AVC. Carriers of G allele had a high risk of Lp(a) ≥ 30 mg/dL (OR= 3.86, CI 95%: 2.2 - 6.7, p=0.001) and AVC (OR= 2.54, CI 95%: 1.56 - 4.14, p=0.001), independently of other CVRF. In this population, carriers of rs10455872-G allele had 3.86 and 2.54 higher risk of Lp(a) ≥ 30 mg/dL or presence of AVC, respectively.