RESUMEN
The occurrence of dyslipidaemia, which is an established risk factor for cardiovascular diseases, has been attributed to multiple factors including genetic and environmental factors. We used a genetic risk score (GRS) to assess the interactions between genetic variants and dietary factors on lipid-related traits in a cross-sectional study of 190 Brazilians (mean age: 21 ± 2 years). Dietary intake was assessed by a trained nutritionist using three 24-h dietary recalls. The high GRS was significantly associated with increased concentration of TAG (beta = 0·10 mg/dl, 95 % CI 0·05-0·16; P < 0·001), LDL-cholesterol (beta = 0·07 mg/dl, 95 % CI 0·04, 0·11; P < 0·0001), total cholesterol (beta = 0·05 mg/dl, 95 % CI: 0·03, 0·07; P < 0·0001) and the ratio of TAG to HDL-cholesterol (beta = 0·09 mg/dl, 95 % CI: 0·03, 0·15; P = 0·002). Significant interactions were found between the high GRS and total fat intake on TAG:HDL-cholesterol ratio (Pinteraction = 0·03) and between the high GRS and SFA intake on TAG:HDL-cholesterol ratio (Pinteraction = 0·03). A high intake of total fat (>31·5 % of energy) and SFA (>8·6 % of energy) was associated with higher TAG:HDL-cholesterol ratio in individuals with the high GRS (beta = 0·14, 95 % CI: 0·06, 0·23; P < 0·001 for total fat intake; beta = 0·13, 95 % CI: 0·05, 0·22; P = 0·003 for SFA intake). Our study provides evidence that the genetic risk of high TAG:HDL-cholesterol ratio might be modulated by dietary fat intake in Brazilians, and these individuals might benefit from limiting their intake of total fat and SFA.
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HDL-Colesterol , Grasas de la Dieta , Humanos , Brasil , Masculino , Femenino , Grasas de la Dieta/administración & dosificación , Adulto Joven , Estudios Transversales , HDL-Colesterol/sangre , Factores de Riesgo , Dislipidemias/genética , Dislipidemias/etiología , Triglicéridos/sangre , LDL-Colesterol/sangre , Predisposición Genética a la Enfermedad , Dieta , Adulto , Polimorfismo de Nucleótido Simple , Adolescente , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/etiología , Puntuación de Riesgo GenéticoRESUMEN
BACKGROUND: Cardiovascular diseases (CVDs) comprise major causes of death worldwide, leading to extensive burden on populations and societies. Alterations in normal lipid profiles, i.e., dyslipidemia, comprise important risk factors for CVDs. However, there is lack of comprehensive evidence on the genetic contribution to dyslipidemia in highly admixed populations. The identification of single nucleotide polymorphisms (SNPs) linked to blood lipid traits in the Brazilian population was based on genome-wide associations using data from the São Paulo Health Survey with Focus on Nutrition (ISA-Nutrition). METHODS: A total of 667 unrelated individuals had genetic information on 330,656 SNPs available, and were genotyped with Axiom™ 2.0 Precision Medicine Research Array. Genetic associations were tested at the 10- 5 significance level for the following phenotypes: low-density lipoprotein cholesterol (LDL-c), very low-density lipoprotein cholesterol (VLDL-c), high-density lipoprotein cholesterol (HDL-c), HDL-c/LDL-c ratio, triglycerides (TGL), total cholesterol, and non-HDL-c. RESULTS: There were 19 significantly different SNPs associated with lipid traits, the majority of which corresponding to intron variants, especially in the genes FAM81A, ZFHX3, PTPRD, and POMC. Three variants (rs1562012, rs16972039, and rs73401081) and two variants (rs8025871 and rs2161683) were associated with two and three phenotypes, respectively. Among the subtypes, non-HDL-c had the highest proportion of associated variants. CONCLUSIONS: The results of the present genome-wide association study offer new insights into the genetic structure underlying lipid traits in underrepresented populations with high ancestry admixture. The associations were robust across multiple lipid phenotypes, and some of the phenotypes were associated with two or three variants. In addition, some variants were present in genes that encode ncRNAs, raising important questions regarding their role in lipid metabolism.
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Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Humanos , Brasil/epidemiología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Lípidos/sangre , Lípidos/genética , LDL-Colesterol/sangre , LDL-Colesterol/genética , Triglicéridos/sangre , Triglicéridos/genética , HDL-Colesterol/sangre , HDL-Colesterol/genética , Dislipidemias/genética , Dislipidemias/sangre , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/epidemiología , FenotipoRESUMEN
This study aimed to investigate metabolism modulation and dyslipidemia in genetic dyslipidemic mice through physical exercise. Thirty-four male C57Bl/6 mice aged 15 months were divided into non-transgenic (NTG) and transgenic overexpressing apoCIII (CIII) groups. After treadmill adaptation, the trained groups (NTG Ex and CIII Ex) underwent an effort test to determine running performance and assess oxygen consumption (VÌO2), before and after the training protocol. The exercised groups went through an 8-week moderate-intensity continuous training (MICT) program, consisting of 40 min of treadmill running at 60% of the peak velocity achieved in the test, three times per week. At the end of the training, animals were euthanized, and tissue samples were collected for ex vivo analysis. ApoCIII overexpression led to hypertriglyceridemia (P<0.0001) and higher concentrations of total plasma cholesterol (P<0.05), low-density lipoprotein (LDL) cholesterol (P<0.01), and very low-density lipoprotein (VLDL) cholesterol (P<0.0001) in the animals. Furthermore, the transgenic mice exhibited increased adipose mass (P<0.05) and higher VÌO2peak compared to their NTG controls (P<0.0001). Following the exercise protocol, MICT decreased triglyceridemia and cholesterol levels in dyslipidemic animals (P<0.05), and reduced adipocyte size (P<0.05), increased muscular glycogen (P<0.001), and improved VÌO2 in all trained animals (P<0.0001). These findings contribute to our understanding of the effects of moderate and continuous exercise training, a feasible non-pharmacological intervention, on the metabolic profile of genetically dyslipidemic subjects.
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Dislipidemias , Consumo de Oxígeno , Condicionamiento Físico Animal , Triglicéridos , Animales , Masculino , Ratones , Dislipidemias/metabolismo , Dislipidemias/terapia , Dislipidemias/genética , Hipertrigliceridemia/terapia , Hipertrigliceridemia/metabolismo , Ratones Endogámicos C57BL , Ratones Transgénicos , Consumo de Oxígeno/fisiología , Condicionamiento Físico Animal/fisiología , Triglicéridos/sangreRESUMEN
INTRODUCTION: In a recent study, we have shown that atorvastatin is clinically safe for dermatomyositis (DM) and antisynthetase syndrome (ASS) patients with dyslipidemia. Herein, we showed in an unprecedented way, the safety of atorvastatin on the muscular tissues of these patients. METHODS: Transcriptome analysis was performed on samples of the vastus lateralis muscle obtained at baseline and after 12 weeks of atorvastatin (20 mg/day) intervention in DM or ASS patients with dyslipidemia [6DM and 5ASS received atorvastatin, and 2DM and 3ASS received placebo]. The results were analyzed considering differences in expression fold change before and after treatment. Histological and histochemical analyses were also performed. RESULTS: In both groups, no significant changes were observed in genes related to the mitochondrial, oxidative, insulin, lipid, and fibrogenic pathways. Histological analysis showed a slight variability in the fiber size that was preserved after the intervention. In addition, the mosaic of muscle fibers was preserved in the internal architecture of the fibers and all histological regions. No fiber necrosis or atrophy, focal failures, subsarcolemmal accumulation, lipids, areas of fibrosis, or alterations in mitochondrial activity were observed. All muscle fibers were labeled for MHC I. CONCLUSION: Atorvastatin did not promote significant changes in the expression of genes related to mitochondrial, oxidative, insulin, lipid, and fibrogenic pathways in the muscle tissues of DM and ASS patients with dyslipidemia. Atorvastatin did not also promote histological and histochemical changes in muscle tissues. Our results reinforce the safety of the administration of atorvastatin to treat dyslipidemia in patients with DM and ASS.
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Dermatomiositis , Dislipidemias , Insulinas , Miositis , Humanos , Atorvastatina/efectos adversos , Dermatomiositis/diagnóstico , Dermatomiositis/tratamiento farmacológico , Miositis/diagnóstico , Miositis/tratamiento farmacológico , Miositis/patología , Músculo Esquelético/patología , Dislipidemias/diagnóstico , Dislipidemias/tratamiento farmacológico , Dislipidemias/genética , Insulinas/uso terapéuticoRESUMEN
Atherogenesis and dyslipidemia increase the risk of cardiovascular disease, which is the leading cause of death in developed countries. While blood lipid levels have been studied as disease predictors, their accuracy in predicting cardiovascular risk is limited due to their high interindividual and interpopulation variability. The lipid ratios, atherogenic index of plasma (AIP = log TG/HDL-C) and the Castelli risk index 2 (CI2 = LDL-C/HDL-C), have been proposed as better predictors of cardiovascular risk, but the genetic variability associated with these ratios has not been investigated. This study aimed to identify genetic associations with these indexes. The study population (n = 426) included males (40%) and females (60%) aged 18-52 years (mean 39 years); the Infinium GSA array was used for genotyping. Regression models were developed using R and PLINK. AIP was associated with variation on APOC3, KCND3, CYBA, CCDC141/TTN, and ARRB1 (p-value < 2.1 × 10-6). The three former were previously associated with blood lipids, while CI2 was associated with variants on DIPK2B, LIPC, and 10q21.3 rs11251177 (p-value 1.1 × 10-7). The latter was previously linked to coronary atherosclerosis and hypertension. KCND3 rs6703437 was associated with both indexes. This study is the first to characterize the potential link between genetic variation and atherogenic indexes, AIP, and CI2, highlighting the relationship between genetic variation and dyslipidemia predictors. These results also contribute to consolidating the genetics of blood lipid and lipid indexes.
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Aterosclerosis , Enfermedad de la Arteria Coronaria , Dislipidemias , Masculino , Femenino , Humanos , Estudios de Casos y Controles , Aterosclerosis/genética , Enfermedad de la Arteria Coronaria/genética , Lípidos , Dislipidemias/genéticaRESUMEN
BACKGROUND AND AIMS: Triglycerides are the initiators of the metabolic changes that lead to atherogenic dyslipidemia (AD). The APOA5 and APOA1 genes are involved in the response and metabolism of serum lipids and lipoproteins, where single nucleotide polymorphisms (SNP) rs662799 (promoter region) and rs5070 (intronic region) have been associated with the susceptibility to dyslipidemia. Until now, few studies evaluate the association of these polymorphisms with the presentation of hypertriglyceridemia and AD among Mexican children. Therefore, the objective was to determine the association between rs662799 and rs5070 with hypertriglyceridemia and AD in a pediatric population of southeastern Mexico. MATERIALS AND METHODS: A case-control analysis was performed including 268 infants aged 2-16 years, anthropometric, clinical variables, and serum lipid profiles were analyzed. DNA was extracted from blood samples and genotyping of polymorphisms was executed with the TaqMan SNP genotyping assay. Allele and genotypic frequencies were calculated. For genetic association analysis, logistic regression models were fitted according to models of inheritance. RESULTS: The SNP rs662799 (C) was significantly associated with hypertriglyceridemia in the overdominant model (OR=3.89, p=0.001) and AD in the dominant model (OR=4.01, p=0.001). The SNP rs5070 (T) has a protective effect against hypertriglyceridemia in the additive risk model (OR=0.68, p=0.03). CONCLUSION: Polymorphism rs662799 was significantly associated with cases of hypertriglyceridemia and AD in minors in southeastern Mexico. On the other hand, rs5070 polymorphism was not associated with cases of hypertriglyceridemia or AD.
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Aterosclerosis , Dislipidemias , Hipertrigliceridemia , Humanos , Niño , México , Apolipoproteína A-V/genética , Genotipo , Hipertrigliceridemia/genética , Polimorfismo de Nucleótido Simple , Aterosclerosis/genética , Dislipidemias/genética , Predisposición Genética a la Enfermedad , Frecuencia de los Genes , TriglicéridosRESUMEN
The purposes of the present study were to analyze liver inflammation and endothelial dysfunction in an experimental model of metabolic syndrome (MS) induced by chronic administration of a sucrose-rich diet (SRD) and to evaluate the effects of chia seed as a therapeutic strategy. Male Wistar rats were fed with a reference diet (RD) for 6 months or a SRD for 3 months. Then, the latter group was randomly divided into two subgroups. One subgroup continued receiving the SRD for up to 6 months and the other was fed with a SRD where whole chia seed was incorporated as a source of dietary fat for the next 3 months (SRD + CHIA). Results showed that rats fed a SRD for a long period of time developed dyslipidemia, hyperglycemia, inflammation and endothelial dysfunction. Hepatic NAS, IL-1ß, NFκB p65, PAI-1, and F4-80 expression, as well as MPO activity were significantly increased and IL-10 expression was significantly decreased; this was accompanied by increased plasma IL-6 and TNF-α levels in rats fed a SRD. In addition, serum and liver nitric oxide (NO) levels and nitric oxide synthase (NOS) were significantly increased in the SRD group. In addition, a significant increase in hepatic iNOS expression and a positive correlation of this with liver NFκB p65 was found. We observed a significant increase in hepatic intercellular adhesion molecule (ICAM), and a negative correlation of this with liver Nrf2 was found. The administration of chia seed for 3 months reversed dyslipidemia, hyperglycemia, inflammation and endothelial dysfunction. In the liver tissue, NAS, IL-1ß, IL-10, NFκB p65, PAI-1, and F4-80 expression and MPO activity were normalized. Serum and liver NO and NOS levels and hepatic iNOS expression were decreased and this last one was associated with a decrease in liver NFκB p65 levels. Hepatic ICAM-1 was normalized and negatively correlated with liver NrF2 levels. This study showed new aspects of liver inflammation and endothelial dysfunction in dyslipidemic insulin resistant rats chronically fed with a sucrose-rich diet. In addition, we demonstrated new properties and molecular mechanisms associated with beneficial effects on inflammation and endothelial dysfunction of chia seed as a therapeutic strategy.
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Dislipidemias , Hepatitis , Hiperglucemia , Síndrome Metabólico , Salvia , Ratas , Masculino , Animales , Interleucina-10/metabolismo , Salvia hispanica , Factor 2 Relacionado con NF-E2/metabolismo , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/genética , Síndrome Metabólico/metabolismo , Ratas Wistar , Inhibidor 1 de Activador Plasminogénico/metabolismo , Semillas/metabolismo , Dislipidemias/tratamiento farmacológico , Dislipidemias/genética , Dislipidemias/metabolismo , Hígado/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Hepatitis/metabolismo , Sacarosa/metabolismo , Modelos Teóricos , Hiperglucemia/metabolismoRESUMEN
The characteristic epigenetic profile of periodontitis found in peripheral leukocytes denotes its impact on systemic immunity. In fact, this profile not only stands for periodontitis as a low-grade inflammatory disease with systemic effects but also as an important source of potentially valuable clinical biomarkers of its systemic effects and susceptibility to other inflammatory conditions. Thus, we aimed to identify relevant genes tested as epigenetic systemic biomarkers in patients with periodontitis, based on the DNA methylation patterns and RNA expression profiles in peripheral immune cells. A detailed protocol was designed following the Preferred Reporting Items for Systematic Review and Meta-analysis -PRISMA guideline. Only cross-sectional and case-control studies that reported potential systemic biomarkers of periodontitis in peripheral immune cell types were included. DNA methylation was analyzed in leukocytes, and gene expression was in polymorphonuclear and mononuclear cells. Hypermethylation was found in TLR regulators genes: MAP3K7, MYD88, IL6R, RIPK2, FADD, IRAK1BP1, and PPARA in early stages of periodontitis, while advanced stages presented hypomethylation of these genes. TGFB1I1, VNN1, HLADRB4, and CXCL8 genes were differentially expressed in lymphocytes and monocytes of subjects with poorly controlled diabetes mellitus, dyslipidemia, and periodontitis in comparison with controls. The DAB2 gene was differentially overexpressed in periodontitis and dyslipidemia. Peripheral blood neutrophils in periodontitis showed differential expression in 163 genes. Periodontitis showed an increase in ceruloplasmin gene expression in polymorphonuclears in comparison with controls. Several genes highlight the role of the epigenetics of peripheral inflammatory cells in periodontitis that could be explored in blood as a source of biomarkers for routine testing.
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Dislipidemias , Periodontitis , Biomarcadores , Ceruloplasmina/genética , Estudios Transversales , Metilación de ADN , Dislipidemias/genética , Expresión Génica , Humanos , Factor 88 de Diferenciación Mieloide/genética , Periodontitis/genética , ARNRESUMEN
The aim of this study was to analyze the liver injury and oxidative stress in an experimental model of Metabolic Syndrome (MS) induced by chronic administration of a sucrose-rich diet (SRD) and to evaluate the effects of chia seed as a therapeutic strategy. Male Wistar rats were fed with a reference diet (RD) -6 months- or a SRD -3 months. Then, the latter group was randomly divided into two subgroups. One subgroup continued receiving the SRD for up to 6 months and the other was fed with a SRD where whole chia seed was incorporated as a source of dietary fat for the next 3 months (SRD+CHIA). The results showed that rats fed with a SRD for a long period of time developed dyslipidemia, hyperglycemia, hepatic lipid accumulation, liver injury, hepatic lipid peroxidation and oxidative stress. Hepatic NrF2 expression was significantly decreased. In addition, a significant increase in hepatic NFκB p65 expression and a positive correlation of this with plasma TNFα levels were found. The administration of chia seed for 3 months reversed dyslipidemia, hyperglycemia, lipid accumulation, liver injury, lipid peroxidation and oxidative stress. In the liver tissue, NrF2 expression was normalized and NFκB p65 expression was decreased, the latter was associated with a decrease in plasma TNFα levels. The present study showed new aspects of liver damage, lipid peroxidation and oxidative stress in dyslipidemic insulin resistant rats chronically fed with a sucrose-rich diet. However, we demonstrated new properties and molecular mechanisms associated with the beneficial anti-oxidant effects of chia seed consumption.
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Dislipidemias , Hiperglucemia , Salvia , Animales , Dieta , Dislipidemias/tratamiento farmacológico , Dislipidemias/genética , Hiperglucemia/metabolismo , Lípidos , Hígado/metabolismo , Masculino , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Estrés Oxidativo , Ratas , Ratas Wistar , Salvia/metabolismo , Salvia hispanica , Semillas/metabolismo , Sacarosa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Dyslipidemias have been linked to an increased risk of adverse health outcomes, including cardiovascular disease, type 2 diabetes, and the metabolic syndrome. Recent reports have associated the beta-carotene oxygenase 1 (BCO1) gene with lipid metabolism, mainly reducing total cholesterol and increasing high-density lipoprotein-cholesterol (HDL-C) concentrations. The hypothesis of this study was that the variant rs6564851 near the BCO1 gene is associated positively with the lipid profile in middle-aged Mexican adults. This study included 1441 Mexicans older than 40 years of age from the Health Workers Cohort Study (HWCS). Genotyping was conducted using a predesigned TaqMan assay. Lipid profile was measured with standardized procedures. Our results showed that the men carrying at least 1 T allele had higher serum triglyceride concentrations than GG homozygous (GG: 146.5 mg/dL; GT: 175 mg/dL; and TT: 184 mg/dL; P = .008). The variant rs6564851 showed a risk associated with the serum triglyceride concentrations(odds ratio [OR], 2.77; P = .002) only in the male group. However, we did not observe significant differences in the serum total cholesterol, HDL-C, and low-density lipoprotein-cholesterol concentrations in both sexes. Our study provides evidence that the variant rs6564851 is negatively associated with the triglyceride concentrations in middle-aged Mexican male adults in the HWCS. This knowledge can be the basis for developing effective nutritional strategies according to sex and the genetic variants present in an individual. Further studies in independent populations are required to validate these findings and determine the mechanism of the association sex dependent.
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Diabetes Mellitus Tipo 2 , Dislipidemias , Triglicéridos , beta-Caroteno 15,15'-Monooxigenasa , Adulto , HDL-Colesterol , Estudios de Cohortes , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/genética , Dislipidemias/sangre , Dislipidemias/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Triglicéridos/sangre , beta-Caroteno 15,15'-Monooxigenasa/sangre , beta-Caroteno 15,15'-Monooxigenasa/genéticaRESUMEN
Dyslipidemia is the main risk factor for coronary artery disease and is characterized by alterations in concentrations of lipids, including low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and triacylglycerols. The participation of several genes in the development of dyslipidemia has been evidenced. Genetic variants in SLC22A1 have been associated with elevated cholesterol and LDL-c levels. The aim of this study was to evaluate the association between single-nucleotide polymorphisms (SNPs) in the SLC22A1 gene with atherogenic risk lipid levels in Mexican women. Anthropometric and biochemical measurements were performed, and four SNPs in SLC22A1 were genotyped by real-time polymerase chain reaction. The Hardy-Weinberg equilibrium was verified, and haplotype frequencies were calculated. We found significant differences between the allele frequencies of the SNPs analyzed with those reported in Mexico and in the world, which could be due to differences in the historical admixture of the women studied. Generalized linear models were evaluated to determine the association between genotypes and haplotypes with lipids levels. We identified a significant increase in total cholesterol and LDL-c levels in women who were carriers of the GA and AG genotypes of the polymorphisms rs628031 and rs594709, respectively, significant effect that is also shown in a dominant inheritance model. Interestingly, we identified an important relationship of the AGC-GAT haplotype with the elevation in LDL-c levels and AGA-GAT haplotype with the elevation in HDL-c levels. On the other hand, we found a strong linkage disequilibrium between the polymorphisms studied. Our results show that variants in the SLC22A1 gene influence serum levels of atherogenic risk lipids, suggesting that these variants probably affect the function of organic cation transporter-1 and therefore, on the regulation of lipid metabolism.
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Aterosclerosis , Proteínas de Transporte de Catecolaminas en la Membrana Plasmática/genética , Dislipidemias , HDL-Colesterol , LDL-Colesterol , Dislipidemias/genética , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , México , Polimorfismo de Nucleótido SimpleRESUMEN
OBJECTIVE: The aim of this study was to develop genetic scores based on single-nucleotide polymorphisms (SNPs) related to lipid metabolism and evaluate whether they used to estimate disturbances in the circulating lipid profile biomarkers of adolescents. METHODS: In a preliminary cross-sectional approach, 113 Brazilian adolescents (10-19 y of age) with cardiovascular disease risk factors were evaluated. Genetic scores from 20 SNPs related to lipid metabolism were calculated by codifying each of them as the rescaled sum of risk allele frequencies. All scores were distributed in classes between 0 (absence of risk alleles) and 10 (presence of all risk alleles) to evaluate the additive effect of risk alleles on the lipid profile outcomes in the same interval. Multiple linear regression analyses were performed to evaluate the association between each score and blood lipid profile biomarkers. RESULTS: Significant associations between genetic scores and unfavorable outcomes in all evaluated lipid profile biomarkers were found. The mean ± SD of the genetic scores for the circulating lipid profile biomarkers in the 0 to 10 scale were 4.4 ± 2 for triacylglycerol, 5.3 ± 1.5 for total cholesterol, 5.6 ± 1.2 for high-density lipoprotein cholesterol, 4.9 ± 1.6 for low-density lipoprotein cholesterol, and 3.6 ± 1.9 for minimally modified low-density lipoprotein cholesterol. For each point obtained in each genetic score, a mean increase ± SE of 15.8 ± 4.2 mg/dL in triacylglycerol (P = 0.0001), 5.3 ± 1.7 mg/dL in total cholesterol (P = 0.0032), 4.8 ± 1.3 mg/dL in low-density lipoprotein cholesterol (P = 0.0003), and 1.1 ± 0.3 U/L in minimally modified low-density lipoprotein cholesterol (P = 0.0020) and a mean decrease of 3.7 ± 0.7 mg/dL in high-density lipoprotein cholesterol (P < 0.0001) concentrations were obtained. CONCLUSION: The calculated genetic scores could be used to estimate disturbances in circulating lipid profile biomarkers of adolescents and be applied in clinical practice to better target interventions to reduce cardiovascular disease risk throughout life.
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Dislipidemias , Lípidos , Adolescente , Biomarcadores/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Dislipidemias/diagnóstico , Dislipidemias/genética , Humanos , Lípidos/sangre , Factores de Riesgo , Triglicéridos/sangreRESUMEN
Polyphenols play a therapeutic role in vascular diseases, acting in inherent illness-associate conditions such as inflammation, diabetes, dyslipidemia, hypertension, and oxidative stress, as demonstrated by clinical trials and epidemiological surveys. The main polyphenol cardioprotective mechanisms rely on increased nitric oxide, decreased asymmetric dimethylarginine levels, upregulation of genes encoding antioxidant enzymes via the Nrf2-ARE pathway and anti-inflammatory action through the redox-sensitive transcription factor NF-κB and PPAR-γ receptor. However, poor polyphenol bioavailability and extensive metabolization restrict their applicability. Polyphenols carried by nanoparticles circumvent these limitations providing controlled release and better solubility, chemical protection, and target achievement. Nano-encapsulate polyphenols loaded in food grade polymers and lipids appear to be safe, gaining resistance in the enteric route for intestinal absorption, in which the mucoadhesiveness ensures their increased uptake, achieving high systemic levels in non-metabolized forms. Nano-capsules confer a gradual release to these compounds, as well as longer half-lives and cell and whole organism permanence, reinforcing their effectiveness, as demonstrated in pre-clinical trials, enabling their application as an adjuvant therapy against cardiovascular diseases. Polyphenol entrapment in nanoparticles should be encouraged in nutraceutical manufacturing for the fortification of foods and beverages. This study discusses pre-clinical trials evaluating how nano-encapsulate polyphenols following oral administration can aid in cardiovascular performance.
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Antioxidantes/farmacología , Cardiotónicos/farmacología , Composición de Medicamentos/métodos , Hipertensión/tratamiento farmacológico , Isquemia Miocárdica/tratamiento farmacológico , Polifenoles/farmacología , Elementos de Respuesta Antioxidante , Antioxidantes/química , Antioxidantes/farmacocinética , Arginina/análogos & derivados , Arginina/antagonistas & inhibidores , Arginina/metabolismo , Cardiotónicos/química , Cardiotónicos/farmacocinética , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Diabetes Mellitus/fisiopatología , Portadores de Fármacos , Dislipidemias/tratamiento farmacológico , Dislipidemias/genética , Dislipidemias/metabolismo , Dislipidemias/fisiopatología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Hipertensión/genética , Hipertensión/metabolismo , Hipertensión/fisiopatología , Isquemia Miocárdica/genética , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatología , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Nanocápsulas/administración & dosificación , Nanocápsulas/química , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Estrés Oxidativo/efectos de los fármacos , Polifenoles/química , Polifenoles/farmacocinética , Transducción de SeñalRESUMEN
Dyslipidemia has a substantial role in the development of acute coronary syndrome (ACS). Previous reports, including genome-wide associations studies (GWAS), have shown that some genetic variants of the proprotein convertase subtilisin-kexin type 7 (PCSK7) gene are associated with plasma lipid levels. In the present study, we evaluated whether PCSK7 gene polymorphisms are significantly associated with the plasma lipid profile and ACS. Three PCSK7 gene polymorphisms (rs508487 T/C, rs236911 C/A, and rs236918 C/G) were determined using TaqMan genotyping assays in a group of 603 ACS patients and 622 healthy controls. The plasma lipid profile was determined in the study groups by enzymatic/colorimetric assays. Under the recessive model, the rs236918 C allele was associated with a high risk of ACS (OR = 2.11, pC = 0.039). In the same way, under the recessive and additive models, the rs236911 C allele was associated with a high risk of ACS (OR = 1.95, pC = 0.037, and OR = 1.28, pC = 0.037, respectively). In addition, under the co-dominant model, the rs508487 T allele was associated with a higher risk of ACS (OR = 1.78, pC = 0.010). The CCC and TCC haplotypes were associated with a high risk of ACS (OR = 1.21, pC = 0.047, and OR = 1.80, pC = 0.001, respectively). The rs236911 CC and rs236918 CC genotypes were associated with lower high-density lipoproteins-cholesterol (HDL-C) plasma concentrations, whereas the rs236911 CC genotype was associated with a higher concentration of triglycerides, as demonstrated in the control individuals who were not receiving antidyslipidemic drugs. Our data suggest that the PCSK7 rs508487 T/C, rs236911 C/A, and rs236918 C/G polymorphisms are associated with the risk of developing ACS, and with plasma concentrations of HDL-C and triglycerides.
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Síndrome Coronario Agudo , HDL-Colesterol/sangre , Dislipidemias , Subtilisinas/genética , Triglicéridos/sangre , Síndrome Coronario Agudo/genética , Síndrome Coronario Agudo/metabolismo , Anciano , Estudios de Casos y Controles , Dislipidemias/genética , Dislipidemias/metabolismo , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Polimorfismo GenéticoRESUMEN
PURPOSE OF REVIEW: To discuss advances on the RNA-targeted therapies to treat dyslipidemia with the aim of reducing atherosclerotic cardiovascular disease (ASCVD). RECENT FINDINGS: Genetic studies have paved the way for therapies that reduce translation of proteins that play causal roles in dyslipidemia and atherosclerosis like proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein B-100 (apoB), apolipoprotein(a) [apo(a)], apolipoprotein C3 (apoC3), and angiopoietin-like 3 (ANGPTL3). Either antisense oligonucleotide (ASO) therapies and small interfering RNA (siRNA) molecules inhibit protein synthesis and consequently improve dyslipidemia. Most of these molecules contain N-acetylgalactosamine (GalNAc) moieties that have high specificity for hepatocytes and therefore reduce concentration in other tissues. Inclisiran, an siRNA for PCSK9, has shown robust LDL-C reductions, with good tolerability, in severe forms of hypercholesterolemia as well as in high cardiovascular disease patients with injections every 3 to 6 months. Pelacarsen is an ASO against apolipoprotein(a) that reduces Lp(a) up to 80% with good tolerability. Either inclisiran or pelacarsen is being tested to show it can prevent ASCVD. AMG 890, an siRNA compound aimed at reducing apo(a) synthesis, is also under investigation. Volanesorsen is an ASO against apoC3 that reduces triglyceride levels up to 70% and is being tested in severe hypertriglyceridemic patients. Vupanorsen is an ASO against ANGPTL3 that reduced triglyceride levels 36-53% among moderate hypertriglyceridemic individuals. Interestingly, it also reduces ApoC3 and non-HDL cholesterol and apoB; however, it lowers HDL cholesterol. RNA-targeted therapies are being extensively tested for dyslipidemia treatment with promising results.
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Aterosclerosis , Dislipidemias , Proteína 3 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina , LDL-Colesterol , Dislipidemias/tratamiento farmacológico , Dislipidemias/genética , Humanos , Proproteína Convertasa 9/genéticaRESUMEN
Childhood obesity is a global and increasing health issue. Inflammation and dysregulated adipose tissue secretion are common findings in obesity and have been related to poor metabolic function. Given that DNA methylation impacts gene expression and is responsive to environmental changes, we aimed, in addition to characterize the patients in anthropometric and biochemical terms, to determine the expression of cytokines and adipokines, assess the methylation on regulatory regions of the genes that code for these molecules, and investigate the association of the expression and gene methylation with anthropometric and biochemical parameters in childhood obesity. Obese children present dyslipidemia, dysregulated serum levels of adipokines and their ratios, altered leukocytic expression of cytokines, and higher methylation at the CXCL8 promoter as compared to the control group. However, no significant results were observed in the fasting plasma glucose levels or the methylation of TGFB1, LEP, and the enhancer region of ADIPOQ. We also found negative correlations of CXCL8 expression with anthropometric and biochemical parameters, and positive correlation of CXCL8 promoter methylation and the serum levels of hepatic enzymes. Our results indicate that changes in metabolic parameters observed in childhood obesity are associated with the expression of adipokines and cytokines, and the methylation status at the CXCL8 promoter. CXCL8 may be a key factor for these alterations, as it correlates with many of the parameters assessed in the present study.
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Antropometría , Metilación de ADN/genética , Interleucina-8/genética , Obesidad Infantil/genética , Obesidad Infantil/metabolismo , Adipoquinas/sangre , Adiponectina/sangre , Proteína C-Reactiva/metabolismo , Niño , Dislipidemias/genética , Femenino , Humanos , Interleucina-8/sangre , Interleucina-8/metabolismo , Leptina/sangre , Hígado/enzimología , Masculino , Obesidad Infantil/sangre , Regiones Promotoras Genéticas/genéticaRESUMEN
Background and Objectives: Coronary artery disease (CAD) is a major health problem in México. The identification of modifiable risk factors and genetic biomarkers is crucial for an integrative and personalized CAD risk evaluation. In this work, we aimed to validate in a Mexican population a set of eight selected polymorphisms previously associated with CAD, myocardial infarction (MI), or dyslipidemia. Materials and Methods: A sample of 907 subjects (394 CAD cases and 513 controls) 40-80 years old was genotyped for eight loci: PSRC1 (rs599839), MRAS (rs9818870), BTN2A1 (rs6929846), MTHFD1L (rs6922269), CDKN2B (rs1333049), KIAA1462 (rs3739998), CXCL12 (rs501120), and HNF1A (rs2259816). The association between single nucleotide polymorphisms (SNPs) and CAD was evaluated by logistic regression models. Results: Multiple logistic regression analysis with adjustment by age, gender, and body mass index showed that rs599839 was significantly associated with CAD (ORADD = 0.72, p = 0.009; ORDOM = 0.66, p = 0.007). Conclusions: The PSRC1 rs599839 polymorphism shows a significant protective association with CAD in this sample of the Mexican population.
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Enfermedad de la Arteria Coronaria/genética , Etnicidad/genética , Fosfoproteínas/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Estudios de Casos y Controles , Dislipidemias/genética , Femenino , Marcadores Genéticos , Estudio de Asociación del Genoma Completo , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Masculino , México , Persona de Mediana Edad , Infarto del Miocardio/genéticaRESUMEN
Type 2 diabetes mellitus (T2DM), dyslipidemia and periodontitis are frequently associated pathologies; however, there are no studies showing the peripheral blood transcript profile of these combined diseases. Here we identified the differentially expressed genes (DEGs) of circulating lymphocytes and monocytes to reveal potential biomarkers that may be used as molecular targets for future diagnosis of each combination of these pathologies (compared to healthy patients) and give insights into the underlying molecular mechanisms of these diseases. Study participants (n = 150) were divided into groups: (H) systemically and periodontal healthy (control group); (P) with periodontitis, but systemically healthy; (DL-P) with dyslipidemia and periodontitis; (T2DMwell-DL-P) well-controlled type 2 diabetes mellitus with dyslipidemia and periodontitis; and (T2DMpoorly-DL-P) poorly-controlled type 2 diabetes mellitus with dyslipidemia and periodontitis. We preprocessed the microarray data using the Robust Multichip Average (RMA) strategy, followed by the RankProd method to identify candidates for DEGs. Furthermore, we performed functional enrichment analysis using Ingenuity Pathway Analysis and Gene Set Enrichment Analysis. DEGs were submitted to pairwise comparisons, and selected DEGs were validated by quantitative polymerase chain reaction. Validated DEGs verified from T2DMpoorly-DL-P versus H were: TGFB1I1, VNN1, HLADRB4 and CXCL8; T2DMwell-DL-P versus H: FN1, BPTF and PDE3B; DL-P versus H: DAB2, CD47 and HLADRB4; P versus H: IGHDL-P, ITGB2 and HLADRB4. In conclusion, we identified that circulating lymphocytes and monocytes of individuals simultaneously affected by T2DM, dyslipidemia and periodontitis, showed an altered molecular profile mainly associated to inflammatory response, immune cell trafficking, and infectious disease pathways. Altogether, these results shed light on novel potential targets for future diagnosis, monitoring or development of targeted therapies for patients sharing these conditions.
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Periodontitis Crónica/genética , Diabetes Mellitus Tipo 2/genética , Dislipidemias/genética , Linfocitos/metabolismo , Monocitos/metabolismo , Adulto , Periodontitis Crónica/complicaciones , Periodontitis Crónica/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Dislipidemias/complicaciones , Dislipidemias/metabolismo , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , TranscriptomaRESUMEN
BACKGROUND: Dyslipidaemias result from the interaction between genetic and environmental factors, including diet disequilibrium and physical inactivity. Among the genetic factors associated with serum lipids, the Taq1B CETP polymorphism has been investigated. The B1 allele has been considered as a risk factor for dyslipidaemia because of its association with greater CETP levels and higher serum triglycerides. The present study aimed to determine the role of the Taq1B polymorphism with lipid and anthropometric variables and its interaction with diet and physical activity. METHODS: In total, 215 subjects were enrolled in this cross-sectional study. Diet intake was evaluated using a 3-day food consumption record and physical activity was determined in accordance with World Health Organization recommendations. The Taq1B CETP polymorphism was determined by allelic discrimination. RESULTS: Subjects with the B1B2/B2B2 genotype, who had a sucrose consumption ≥5% of the total kcal day-1 , had higher levels of total cholesterol (TC) [165.55 (142.21-188.89) mg dL-1 versus 200.19 (184.79-215.60) mg dL-1 ; P for interaction = 0.034] and low-density lipoprotein [99.29 (75.52-123.05) mg dL-1 versus 128.64 (113.59-143.69) mg dL-1 ; P for interaction = 0.037] than subjects with the B1B1 genotype. Subjects who did not perform physical activity and had the B1B2/B2B2 genotype showed significantly higher levels of TC [177.48 (161.36-193.60) mg dL-1 versus 194.49 (185.43-203.56) mg mL-1 ; P for interaction = 0.033] than subjects with the B1B1 genotype. CONCLUSIONS: We provide evidence that subjects with inadequate environmental factors carriers of the polymorphic genotype had higher serum lipid levels than subjects with the B1B1 genotype.
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Proteínas de Transferencia de Ésteres de Colesterol/genética , Sacarosa en la Dieta/efectos adversos , Ingestión de Alimentos/genética , Lípidos/sangre , Conducta Sedentaria , Adulto , Alelos , Indio Americano o Nativo de Alaska/genética , Antropometría , Estudios Transversales , Dieta/efectos adversos , Registros de Dieta , Dislipidemias/genética , Femenino , Genotipo , Humanos , Masculino , México/etnología , Polimorfismo Genético , Factores de RiesgoRESUMEN
Dyslipidemias are common risk factors for the development of chronic disorders including type 2 diabetes (T2D). Over 100 associated loci have been identified but few reports have evaluated the population attributable fraction captured by them in population-based nationwide surveys. Therefore, we determined the population contribution of a set of known genetic risk variants to the development of dyslipidemias and T2D in Mexico. This study included 1665 participants from a Mexican National Health Survey carried out in the year 2000. It is a probabilistic complex sample survey of households, which comprises representative data at a national level. 103 previously reported SNPs associated with different dyslipidemias or T2D were genotyped and used to compute polygenic risk scores. We found that the previously known variants associated with dyslipidemias explain at most 7% of the total risk variance of lipid levels. In contrast, the known genetic risk component for T2D explained a negligible amount of variance (0.1%). Notably, variants derived from the Native-American ancestry have the strongest effect and contribute with a high proportion of the variance. These results support the need for additional studies aimed to identify specific genetic risk variants for Mexican population.