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BACKGROUND AND OBJECTIVE: Cardiovascular diseases are the leading death cause in Europe and entail large treatment costs. Cardiovascular risk prediction is crucial for the management and control of cardiovascular diseases. Based on a Bayesian network built from a large population database and expert judgment, this work studies interrelations between cardiovascular risk factors, emphasizing the predictive assessment of medical conditions, and providing a computational tool to explore and hypothesize such interrelations. METHODS: We implement a Bayesian network model that considers modifiable and non-modifiable cardiovascular risk factors as well as related medical conditions. Both the structure and the probability tables in the underlying model are built using a large dataset collected from annual work health assessments as well as expert information, with uncertainty characterized through posterior distributions. RESULTS: The implemented model allows for making inferences and predictions about cardiovascular risk factors. The model can be utilized as a decision- support tool to suggest diagnosis, treatment, policy, and research hypothesis. The work is complemented with a free software implementing the model for practitioners' use. CONCLUSIONS: Our implementation of the Bayesian network model facilitates answering public health, policy, diagnosis, and research questions concerning cardiovascular risk factors.
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Enfermedades Cardiovasculares , Humanos , Teorema de Bayes , Factores de Riesgo , Programas Informáticos , Factores de Riesgo de Enfermedad CardiacaAsunto(s)
Androstenos/efectos adversos , Desensibilización Inmunológica , Hipersensibilidad a las Drogas/inmunología , Hipersensibilidad a las Drogas/terapia , Androstenos/administración & dosificación , Biomarcadores , Desensibilización Inmunológica/efectos adversos , Desensibilización Inmunológica/métodos , Hipersensibilidad a las Drogas/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Pruebas Cutáneas , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND AND AIMS: Fermented dairy products have been associated with a better diet quality and cardio-metabolic profile. However, in Mediterranean populations, these associations have not been well characterized. The aim of this study was to assess the diet quality and the associations between the consumption of total fermented dairy products and their subtypes and the prevalence of Metabolic Syndrome (MetS) components in a Mediterranean population at high cardiovascular risk. METHODS AND RESULTS: Baseline cross-sectional analyses were conducted on 6,572 men and women (mean age: 65 years) with overweight or obesity and MetS recruited into the PREDIMED-Plus cohort. A 143-item Food Frequency Questionnaire (FFQ) was used, and anthropometrical, biochemical, and blood pressure measurements were recorded. Multivariate-adjusted Cox regressions were fitted to analyze the association between quartiles of consumption of fermented dairy products and their subtypes and MetS components to estimate the relative risk (RR) and 95% confidence intervals (95% CIs). Participants who were high consumers of fermented dairy products reported a higher consumption of fruit, vegetables, fish, nuts, and whole bread and a lower consumption of white bread, alcohol, and cookies. Participants in the higher quartile showed a lower prevalence of the low HDL-cholesterol component of the MetS (RR=0.88; 95% CI: 0.78-0.98) than those in the lowest quartile of cheese consumption. Cheese consumption was inversely associated with the prevalence of hypertriglyceridemia. Total fermented dairy products, yogurt, and its types were not associated with any of the MetS components. CONCLUSIONS: Compared to nonconsumers, participants consuming fermented dairy products reported a better diet quality and, particularly, cheese consumers presented a lower prevalence of hypertriglyceridemia and low HDL-cholesterol plasma levels, which are MetS components.
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Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Productos Lácteos Cultivados , Dieta Saludable , Síndrome Metabólico/epidemiología , Síndrome Metabólico/prevención & control , Anciano , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Queso , HDL-Colesterol/sangre , Estudios Transversales , Encuestas sobre Dietas , Femenino , Humanos , Hipertrigliceridemia/sangre , Hipertrigliceridemia/epidemiología , Hipertrigliceridemia/prevención & control , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/diagnóstico , Persona de Mediana Edad , Valor Nutritivo , Tamaño de la Porción , Prevalencia , Factores Protectores , Ingesta Diaria Recomendada , Factores de Riesgo , Conducta de Reducción del Riesgo , España , Triglicéridos/sangreRESUMEN
BACKGROUND AND AIMS: Two weight gain prevention strategies, one targeting small changes to diet and physical activity and a second targeting large changes, significantly reduced weight gain in young adulthood. We examined whether weight gain prevention blunts genetic risk for body weight increase and/or high density lipoprotein cholesterol (HDL-C) lowering over two years. METHODS AND RESULTS: Participants were 524 male and female young adults (mean age = 28.2, SD = 4.3; mean BMI = 25.5, SD = 2.6). Obesity-related SNPs accounting for ≥ 0.04% of the variance were genotyped and combined into a genetic risk score. For HDL-C, SNPs within CETP, LIPC and FADS2 were genotyped. The obesity-related genetic risk score did not predict change in BMI independently or in interaction with treatment arm. However, consistent with the prior literature, each copy of the HDL-C risk, C, allele at CETP rs3764261 was associated with lower HDL-C at baseline. Moreover, significant interaction between SNP and treatment arm for change in HDL-C was observed (p = 0.02). In the control group, HDL-C change was dependent upon rs3764261 (p = 0.004) with C allele carriers showing a continued reduction in HDL-C. In contrast, within the two intervention groups, HDL-C increased on average with no differential effect of rs3764261 (p > 0.24). Notably, even among carriers of the CC genotype, small and large change arms were associated with increased HDL-C and the control arm a reduction (p = 0.013). CONCLUSIONS: The C allele at CETP rs3764261 is a strong risk factor for low HDL-C in young adulthood but weight gain prevention may mitigate this risk. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: clinicaltrials.gov Identifier: NCT01183689, https://clinicaltrials.gov/.
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Proteínas de Transferencia de Ésteres de Colesterol/genética , HDL-Colesterol/sangre , Dislipidemias/genética , Dislipidemias/prevención & control , Obesidad/prevención & control , Polimorfismo de Nucleótido Simple , Aumento de Peso/genética , Adolescente , Adulto , Factores de Edad , Biomarcadores/sangre , Índice de Masa Corporal , Dislipidemias/sangre , Dislipidemias/diagnóstico , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Obesidad/sangre , Obesidad/diagnóstico , Obesidad/genética , Fenotipo , Factores de Riesgo , Estados Unidos , Adulto JovenRESUMEN
The hepatic lipase (LIPC) locus is a well-established determinant of high-density lipoprotein cholesterol (HDL-C) concentrations, an association that is modified by dietary fat in observational studies. Dietary interventions are lacking. We investigated dietary modulation of LIPC rs1800588 (-514 C/T) for lipids and glucose using a randomized crossover design comparing a high-fat Western diet and a low-fat traditional Hispanic diet in individuals of Caribbean Hispanic descent (n = 42, 4 wk/phase). No significant gene-diet interactions were observed for HDL-C. However, differences in dietary response according to LIPC genotype were observed. In major allele carriers (CC/CT), HDL-C (mmol/l) was higher following the Western diet compared with the Hispanic diet: phase 1 (Western: 1.3 ± 0.03; Hispanic: 1.1 ± 0.04; P = 0.0004); phase 2 (Western: 1.4 ± 0.03; Hispanic: 1.2 ± 0.03; P = 0.0003). In contrast, HDL-C in TT individuals did not differ by diet. Only major allele carriers benefited from the higher-fat diet for HDL-C. Secondarily, we explored dietary fat quality and rs1800588 for HDL-C and triglycerides (TG) in a Boston Puerto Rican Health Study (BPRHS) subset matched for diabetes and obesity status (subset n = 384). In the BPRHS, saturated fat was unfavorably associated with HDL-C and TG in rs1800588 TT carriers. LIPC rs1800588 appears to modify plasma lipids in the context of dietary fat. This new evidence of genetic modulation of dietary responses may inform optimal and personalized dietary fat advice and reinforces the importance of studying genetic markers in diet and cardiometabolic health.
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HDL-Colesterol/sangre , Grasas de la Dieta/farmacología , Lipasa/genética , Adulto , HDL-Colesterol/genética , Estudios Transversales , Dieta Alta en Grasa/efectos adversos , Femenino , Prueba de Tolerancia a la Glucosa , Hispánicos o Latinos , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Puerto RicoRESUMEN
Lipid traits (total, low-density and high-density lipoprotein cholesterol, and triglycerides) are risk factors for cardiovascular disease. DNA methylation is not only an inherited but also modifiable epigenetic mark that has been related to cardiovascular risk factors. Our aim was to identify loci showing differential DNA methylation related to serum lipid levels. Blood DNA methylation was assessed using the Illumina Human Methylation 450 BeadChip. A two-stage epigenome-wide association study was performed, with a discovery sample in the REGICOR study (n = 645) and validation in the Framingham Offspring Study (n = 2,542). Fourteen CpG sites located in nine genes (SREBF1, SREBF2, PHOSPHO1, SYNGAP1, ABCG1, CPT1A, MYLIP, TXNIP and SLC7A11) and 2 intergenic regions showed differential methylation in association with lipid traits. Six of these genes and 1 intergenic region were new discoveries showing differential methylation related to total cholesterol (SREBF2), HDL-cholesterol (PHOSPHO1, SYNGAP1 and an intergenic region in chromosome 2) and triglycerides (MYLIP, TXNIP and SLC7A11). These CpGs explained 0.7%, 9.5% and 18.9% of the variability of total cholesterol, HDL cholesterol and triglycerides in the Framingham Offspring Study, respectively. The expression of the genes SREBF2 and SREBF1 was inversely associated with methylation of their corresponding CpGs (P-value = 0.0042 and 0.0045, respectively) in participants of the GOLDN study (n = 98). In turn, SREBF1 expression was directly associated with HDL cholesterol (P-value = 0.0429). Genetic variants in SREBF1, PHOSPHO1, ABCG1 and CPT1A were also associated with lipid profile. Further research is warranted to functionally validate these new loci and assess the causality of new and established associations between these differentially methylated loci and lipid metabolism.
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Enfermedades Cardiovasculares/genética , Islas de CpG , Metilación de ADN , Epigénesis Genética , Sitios Genéticos , Metabolismo de los Lípidos/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/metabolismo , Sistema de Transporte de Aminoácidos y+/genética , Sistema de Transporte de Aminoácidos y+/metabolismo , Enfermedades Cardiovasculares/enzimología , Enfermedades Cardiovasculares/metabolismo , Carnitina O-Palmitoiltransferasa/genética , Carnitina O-Palmitoiltransferasa/metabolismo , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Colesterol/sangre , Colesterol/química , Colesterol/metabolismo , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Monoéster Fosfórico Hidrolasas/genética , Monoéster Fosfórico Hidrolasas/metabolismo , Análisis de Secuencia de ADN , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteína 2 de Unión a Elementos Reguladores de Esteroles/genética , Proteína 2 de Unión a Elementos Reguladores de Esteroles/metabolismo , Triglicéridos/sangre , Triglicéridos/genética , Triglicéridos/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Proteínas Activadoras de ras GTPasa/genética , Proteínas Activadoras de ras GTPasa/metabolismoRESUMEN
BACKGROUND AND AIMS: Subclinical thyroid conditions, defined by normal thyroxin (T4) but abnormal thyroid-stimulating hormone (TSH) levels, may be associated with cardiovascular and metabolic risk. More recently, TSH levels within the normal range have been suggested to be associated with metabolic syndrome and cardiovascular risk. This work studies the linearity of the relationship between metabolic syndrome and TSH across the euthyroid range. METHODS AND RESULTS: We studied 3533 male participants of the Aragon Workers' Health Study (AWHS) with normal TSH and free T4 levels, across quintiles of these variables, after adjusting for age, alcohol intake, and smoking. Compared with the lowest TSH quintile, the odds ratios for metabolic syndrome at the higher quintiles, which indicate lower thyroid function, were 1.34 (1.04, 1.73), 1.56 (1.21, 2.01), 1.57 (1.22, 2.03), and 1.71 (1.32, 2.21). The lowest free T4 quintile also showed an odds ratio of 1.49 (1.16, 1.90) with respect to the highest quintile. In addition, spline models showed departures from linearity: the risk of metabolic syndrome mostly increases at TSH values below the median (sample half-closest to subclinical hyperthyroidism). Interestingly, glucose also increases with TSH primarily below the median TSH, diastolic blood pressure shows similar changes across the entire TSH range, whereas body mass index, triglycerides, and high-density lipoprotein (HDL)-cholesterol change only at the highest normal TSH values, which are associated with lower free T4 concentration. CONCLUSIONS: TSH and free T4 within the normal range are associated with the metabolic syndrome. The sample half-below the TSH median (with probably higher functional thyroid status) exhibited better metabolic and cardiovascular profiles.
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Glucemia/análisis , Índice de Masa Corporal , Síndrome Metabólico/sangre , Síndrome Metabólico/epidemiología , Tirotropina/sangre , Adulto , Factores de Edad , Determinación de la Presión Sanguínea , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/fisiopatología , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Intervalos de Confianza , Estudios Transversales , Humanos , Incidencia , Modelos Lineales , Modelos Logísticos , Masculino , Síndrome Metabólico/fisiopatología , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Medición de Riesgo , Índice de Severidad de la Enfermedad , España/epidemiologíaRESUMEN
BACKGROUND & AIMS: To test several circadian rhythm variables in a female population to identify the best tool to assess chronodisruption in obesity and metabolic syndrome (MetS) to define a score to be used for chronodisruption characterization in clinical practice. METHODS: Anthropometric measurements and markers of circadian rhythms, such as sleep and feeding diary, Horne-Ostberg questionnaire, melatonin and cortisol measurements, and wrist temperature measurements, were determined. MetS variables were also analyzed. Study was conducted in 70 women. Data were subjected to factor analysis. Receiver operating characteristic curves were used as predictors of chronodisruption risk, and a score was calculated to classify the subjects of risk. RESULTS: Factor analysis showed that the first-factor grouped variables were related to the skin temperature measurement. Second factor consisted of variables related to salivary cortisol levels and obesity-related measurements. Third factor included variables related to sleep-wake cycle. Fourth factor referred to peripheral temperature variables and included the classification of subjects according to the Horne-Ostberg questionnaire. To obtain a final punctuation we performed the weighted mean of the first four factors. The final range was from 27 to 57, mean value of 42. Punctuation was defined as the "chronodisruption score." Women displaying higher chronodisruption scores had higher MetS risk. CONCLUSION: The study demonstrates that wrist temperature recordings, together with two questions of sleep onset and offset, and one morning salivary cortisol determination could be enough to characterize the chronobiology of obesity and MetS, a new chronodisruption score was developed.
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Fenómenos Cronobiológicos , Síndrome Metabólico/sangre , Obesidad/sangre , Adiponectina/sangre , Adulto , Biomarcadores/sangre , Glucemia/metabolismo , Índice de Masa Corporal , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Ritmo Circadiano , Análisis Factorial , Femenino , Humanos , Hidrocortisona/sangre , Leptina/sangre , Melatonina/sangre , Persona de Mediana Edad , Sueño , Encuestas y Cuestionarios , Triglicéridos/sangreRESUMEN
BACKGROUND AND AIMS: Lipoprotein lipase (LPL) is a candidate gene for obesity based on its role in triglyceride hydrolysis and the partitioning of fatty acids towards storage or oxidation. Whether dietary fatty acids modify LPL associated obesity risk is unknown. METHODS AND RESULTS: We examined five single nucleotide polymorphisms (SNPs) (rs320, rs2083637, rs17411031, rs13702, rs2197089) for potential interaction with dietary fatty acids for obesity traits in 1171 participants (333 men and 838 women, aged 45-75 y) of the Boston Puerto Rican Health Study (BPRHS). In women, SNP rs320 interacted with dietary polyunsaturated fatty acids (PUFA) for body mass index (BMI) (P = 0.002) and waist circumference (WC) (P = 0.001) respectively. Higher intake of PUFA was associated with lower BMI and WC in homozygotes of the major allele (TT) (P = 0.01 and 0.005) but not in minor allele carriers (TG and GG). These interactions were replicated in an independent population, African American women of the Atherosclerosis Risk in Communities (ARIC) study (n = 1334). CONCLUSION: Dietary PUFA modulated the association of LPL rs320 with obesity traits in two independent populations. These interactions may be relevant to the dietary management of obesity, particularly in women.
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Ácidos Grasos Insaturados/sangre , Lipoproteína Lipasa/genética , Lipoproteína Lipasa/metabolismo , Obesidad/enzimología , Obesidad/genética , Anciano , Anciano de 80 o más Años , Aterosclerosis/epidemiología , Índice de Masa Corporal , Boston , Dieta , Conducta Alimentaria , Femenino , Hispánicos o Latinos , Humanos , Indígenas Norteamericanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Polimorfismo de Nucleótido Simple/genética , Población BlancaRESUMEN
OBJECTIVES: Some of the major challenges associated with successful dietary weight management include the identification of individuals not responsive to specific interventions. The aim was to investigate the potential relationship between weight loss and circadian rhythmicity, using wrist temperature and actimetry measurements, in women undergoing a weight-loss program, in order to assess whether circadian rhythmicity could be a marker of weight-loss effectiveness. METHODS: Participants were 85 overweight and obese women (body mass index, BMI: 30.24±4.95 kg m(-2)) subjected to a weight-reduction program. Efficacy of the treatment was defined as total weight loss, percentage of initial weight and weekly weight loss rates. Circadian rhythmicity in wrist temperature motor activity and position were analyzed using different sensors. RESULTS: Lower weight loss was related with a more flattened pattern measured as amplitude from cosinor (r=0.235, P=0.032), a higher fragmentation of rhythms determined by higher intradaily variability (IV) (r=-0.339, P=0.002), and an impaired wrist temperature circadian rhythm determined by the means of Circadian Function Index (r=0.228, P=0.038). Further analyses showed that low responders displayed lower amplitude (0.71±0.36 versus 1.24±0.62, P=0.036) and higher fragmentation of the circadian rhythm (0.24±0.11 versus 0.15±0.07, P=0.043) than high responders. Whereas we did not find significant differences in total activity rates between high responders and low responders, we found significant differences for the mean values of body position for high responders (39.12±3.79°) as compared with low responder women (35.31±2.53°, P=0.01). CONCLUSIONS: Circadian rhythms at the beginning of the treatment are good predictors of future weight loss. Further treatment should consider chronobiological aspects to diagnose obesity and effectiveness of treatments.
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Temperatura Corporal , Ritmo Circadiano , Actividad Motora , Obesidad/prevención & control , Pérdida de Peso , Programas de Reducción de Peso , Muñeca , Adulto , Terapia Conductista , Índice de Masa Corporal , Dieta Mediterránea , Femenino , Humanos , Obesidad/metabolismo , Valor Predictivo de las Pruebas , España , Resultado del Tratamiento , Muñeca/irrigación sanguíneaRESUMEN
Current treatments for losing weight based mainly on diet and exercise are, in general, unsuccessful. So, as an alternative to the general strategy of one-size-fits-all, a more individualized approach is proposed through the so-called Personalised Medicine in which genotype data are used to personalize treatment and to optimize the results. This paper examines the current situation of the evidence on the influence of the genotype in modulating the association between diet or exercise on obesity and weight-related measures. Most of these studies are observational studies, as there are far fewer experimental ones assessing short-term weight-loss or its long-term maintenance. Many more studies are therefore required for that purpose. Having reviewed the results of the studies undertaken to date, we can say that huge progress has been made in identifying polymorphisms in genes related with obesity and that there is a great consistency of the influence of the FTO gene on the same, while for other variants, there is less consistency. Moreover, the results on gene-diet and gene-physical activity interactions in determining obesity phenotypes are very heterogeneous, so an important recommendation is to standardize the methodology for undertaking these studies. Furthermore, an important lack of replication has been observed suggesting undetected higher-level interactions and/or experimental caveats. Therefore, the current evidence level of applying genotype data to obesity treatment is at its early stages. Nevertheless, future prospects are encouraging and to make this come true, several guidelines are proposed for carrying out new studies on applications in clinical practice.
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Genotipo , Obesidad/terapia , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Ensayos Clínicos como Asunto , Dieta Reductora , Terapia por Ejercicio , Predicción , Interacción Gen-Ambiente , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Variación Genética , Humanos , Obesidad/dietoterapia , Obesidad/genética , Obesidad/prevención & control , Estudios Observacionales como Asunto , Polimorfismo de Nucleótido Simple , Guías de Práctica Clínica como Asunto , Medicina de Precisión/tendencias , Proteínas/genética , Proteínas/fisiología , Proyectos de Investigación , TranscriptomaRESUMEN
BACKGROUND AND AIMS: In vitro studies suggest that low density lipoprotein receptor-related protein 1 (LRP1) plays a role in the secondary uptake of chylomicrons. In addition, in vivo studies using LRP-1 knockout mice show these animals exhibit delayed chylomicron clearance. Whether this is true in humans is unknown. We aimed to determine whether genetic variants in LRP-1 are associated with postprandial chylomicron uptake in humans given an oral fat challenge. METHODS AND RESULTS: As many as 817 men and women (mean age +/- standard deviation = 48.4 +/- 16.4 years) forming the study population for the Genetics of Lipid Lowering Drugs Network (GOLDN) study ingested an oral fat load of 700 kilocalories per m² of body surface area at 83% fat, after an 8-h fast. Chylomicrons were measured by nuclear resonance spectroscopy (NMR) at fasting, and 3.5 and 6 h after the meal. 26 Single nucleotide polymorphisms (SNPs) in the LRP-1 gene were genotyped on the Affymetrix 6.0 array. Chylomicrons were, as expected, zero at fasting. Mixed linear models adjusted for age, sex, study site and pedigree tested for associations between LRP-1 SNPs and changes in chylomicron concentrations 3.5-6 h. A gene-based test across all 26 SNPs was conducted which corrected for the linkage disequilibrium (LD) between SNPs. 11 LRP-1 SNPs were significantly associated with the change in chylomicron concentration correction for multiple testing (Q < 0.05). The subsequent gene-based test, was also significant (P = 0.01). CONCLUSION: These results require replication but strongly indicate the role of LRP1 in postprandial lipoprotein uptake and/or clearance.
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Quilomicrones/metabolismo , Dieta Alta en Grasa/efectos adversos , Grasas de la Dieta/metabolismo , Absorción Intestinal , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Comidas , Polimorfismo de Nucleótido Simple , Adulto , Alelos , Quilomicrones/sangre , Femenino , Estudios de Asociación Genética , Humanos , Desequilibrio de Ligamiento , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Minnesota , Análisis de Secuencia por Matrices de Oligonucleótidos , Periodo Posprandial , UtahRESUMEN
BACKGROUND: There is emerging literature demonstrating a relationship between the timing of feeding and weight regulation in animals. However, whether the timing of food intake influences the success of a weight-loss diet in humans is unknown. OBJECTIVE: To evaluate the role of food timing in weight-loss effectiveness in a sample of 420 individuals who followed a 20-week weight-loss treatment. METHODS: Participants (49.5% female subjects; age (mean ± s.d.): 42 ± 11 years; BMI: 31.4 ± 5.4 kg m(-2)) were grouped in early eaters and late eaters, according to the timing of the main meal (lunch in this Mediterranean population). 51% of the subjects were early eaters and 49% were late eaters (lunch time before and after 1500 hours, respectively), energy intake and expenditure, appetite hormones, CLOCK genotype, sleep duration and chronotype were studied. RESULTS: Late lunch eaters lost less weight and displayed a slower weight-loss rate during the 20 weeks of treatment than early eaters (P=0.002). Surprisingly, energy intake, dietary composition, estimated energy expenditure, appetite hormones and sleep duration was similar between both groups. Nevertheless, late eaters were more evening types, had less energetic breakfasts and skipped breakfast more frequently that early eaters (all; P<0.05). CLOCK rs4580704 single nucleotide polymorphism (SNP) associated with the timing of the main meal (P=0.015) with a higher frequency of minor allele (C) carriers among the late eaters (P=0.041). Neither sleep duration, nor CLOCK SNPs or morning/evening chronotype was independently associated with weight loss (all; P>0.05). CONCLUSIONS: Eating late may influence the success of weight-loss therapy. Novel therapeutic strategies should incorporate not only the caloric intake and macronutrient distribution - as is classically done - but also the timing of food.
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Conducta Alimentaria , Obesidad/dietoterapia , Pérdida de Peso , Programas de Reducción de Peso/métodos , Adulto , Índice de Masa Corporal , Proteínas CLOCK/genética , Ritmo Circadiano , Dieta Mediterránea , Ingestión de Energía , Metabolismo Energético , Femenino , Genotipo , Ghrelina/sangre , Humanos , Leptina/sangre , Masculino , Obesidad/sangre , Obesidad/epidemiología , Valor Predictivo de las Pruebas , Sueño , España/epidemiología , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Pérdida de Peso/genéticaRESUMEN
OBJECTIVE: Low-density lipoprotein-related receptor protein 1 (LRP1) is a multi-functional endocytic receptor and signaling molecule that is expressed in adipose and the hypothalamus. Evidence for a role of LRP1 in adiposity is accumulating from animal and in vitro models, but data from human studies are limited. The study objectives were to evaluate (i) relationships between LRP1 genotype and anthropometric traits, and (ii) whether these relationships were modified by dietary fatty acids. DESIGN AND METHODS: We conducted race/ethnic-specific meta-analyses using data from 14 studies of US and European whites and 4 of African Americans to evaluate associations of dietary fatty acids and LRP1 genotypes with body mass index (BMI), waist circumference and hip circumference, as well as interactions between dietary fatty acids and LRP1 genotypes. Seven single-nucleotide polymorphisms (SNPs) of LRP1 were evaluated in whites (N up to 42 000) and twelve SNPs in African Americans (N up to 5800). RESULTS: After adjustment for age, sex and population substructure if relevant, for each one unit greater intake of percentage of energy from saturated fat (SFA), BMI was 0.104 kg m(-2) greater, waist was 0.305 cm larger and hip was 0.168 cm larger (all P<0.0001). Other fatty acids were not associated with outcomes. The association of SFA with outcomes varied by genotype at rs2306692 (genotyped in four studies of whites), where the magnitude of the association of SFA intake with each outcome was greater per additional copy of the T allele: 0.107 kg m(-2) greater for BMI (interaction P=0.0001), 0.267 cm for waist (interaction P=0.001) and 0.21 cm for hip (interaction P=0.001). No other significant interactions were observed. CONCLUSION: Dietary SFA and LRP1 genotype may interactively influence anthropometric traits. Further exploration of this, and other diet x genotype interactions, may improve understanding of interindividual variability in the relationships of dietary factors with anthropometric traits.
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Población Negra , Ácidos Grasos/metabolismo , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad , Obesidad/genética , Polimorfismo de Nucleótido Simple , Población Blanca , Tejido Adiposo , Adulto , Anciano , Anciano de 80 o más Años , Población Negra/genética , Índice de Masa Corporal , Europa (Continente)/epidemiología , Femenino , Frecuencia de los Genes , Interacción Gen-Ambiente , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Fenotipo , Prevalencia , Estados Unidos/epidemiología , Población Blanca/genéticaRESUMEN
INTRODUCTION: Genetics is behind our circadian machinery. CLOCK (Circadian Locomotor Output Cycles Kaput) 3111T/C single-nucleotide polymorphism (SNP) has been previously related to obesity and weight loss. However, phenotypic association and functionality of CLOCK 3111 locus is still unknown. The aim of this study was to determine, in free-living conditions, if the presence of CLOCK 3111C in overweight women could be related to (a) circadian disorders, and (b) changes in sleep quality, to improve understanding of the previously demonstrated associations with obesity and reduced weight loss of the C carriers. METHODS: Wrist temperature, actimetry and position (TAP) and TAP variables were measured as markers of circadian functionality during 8 consecutive days. A rest-activity and food diary was also completed, whereas sleep quality was determined by domiciliary polysomnography. We recruited 85 women who were overweight with body mass index (BMI) of 28.59±4.30 kg m(-2) and age 43±12 years. From this sample, we found that 43 women were carrying the minor allele (C) for CLOCK 3111T/C SNP and 42 women were TT carriers (major allele carriers). Both groups of patients were matched for number, age, obesity parameters and energy intake. RESULTS: Compared with TT subjects, who showed more robust circadian rhythm profiles, patients with the C allele displayed significant circadian abnormalities: lower amplitude and greater fragmentation of the rhythm, a less stable circadian pattern and a significantly weakened circadian function, as assessed by the circadian function index (CFI). C subjects were also less active, started their activities later in the morning and were sleepier during the day, showing a delayed acrophase that characterizes 'evening-type' subjects. CONCLUSION: C genetic variants in CLOCK 3111T/C display a less robust circadian rhythm than TT and a delayed acrophase that characterizes 'evening-type' subjects. We support the notion that identifying CLOCK genotypes in patients may assist the therapist in characterization of the roots of the metabolic problem.
Asunto(s)
Proteínas CLOCK/genética , Ritmo Circadiano/genética , Obesidad/genética , Polimorfismo de Nucleótido Simple , Trastornos del Sueño-Vigilia/genética , Adulto , Femenino , Frecuencia de los Genes , Variación Genética , Genotipo , Humanos , Persona de Mediana Edad , Obesidad/epidemiología , Polisomnografía , Sueño , Trastornos del Sueño-Vigilia/epidemiología , España/epidemiología , Encuestas y Cuestionarios , Termometría , Pérdida de PesoRESUMEN
As a peroxisome proliferator-activated receptor alpha (PPARα) agonist, fenofibrate favorably modulates dyslipidemia and inflammation markers, which are associated with cardiovascular risk. To determine whether variation in the PPARα receptor gene was associated with lipid and inflammatory marker response, we conducted a 3-week trial of fenofibrate in 861 men and women. Mixed linear models that controlled for age and sex, as well as family pedigree and study center, were constructed using single-nucleotide polymorphisms (SNPs) in the PPARα gene as predictors and changes in fasting triglycerides (TGs), cholesterol and inflammatory markers as outcomes. Significant associations with low-density cholesterol and interleukin-2 (P<0.001) responses to fenofibrate were found. Although there were suggestive associations with tumor necrosis factor-alpha and TG responses (P<0.05), these did not survive the correction for multiple testing. We conclude that variants in the PPARα gene may contribute to future pharmacogenomic paradigms seeking to predict fenofibrate responders from both an anti-dyslipidemic and anti-inflammatory perspective.
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LDL-Colesterol/genética , Fenofibrato/administración & dosificación , Lípidos/genética , PPAR alfa/genética , Adulto , Anciano , LDL-Colesterol/sangre , Femenino , Estudios de Asociación Genética , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Triglicéridos/sangre , Triglicéridos/genética , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
BACKGROUND AND AIMS: Adiponectin is an adipose-secreted protein that has been linked to changes in insulin sensitivity, high-density lipoprotein cholesterol levels, and inflammatory patterns. Although fenofibrate therapy can raise adiponectin levels, treatment response is heterogeneous and heritable, suggesting a role for genetic mediators. This is the first genome-wide association study of fenofibrate effects on circulating adiponectin. METHODS AND RESULTS: Plasma adiponectin was measured in participants of the Genetics of Lipid Lowering Drugs and Diet Network (n = 793) before and after a 3-week daily treatment with 160 mg of fenofibrate. Associations between variants on the Affymetrix Genome-Wide Human SNP Array 6.0 and adiponectin were assessed using mixed linear models, adjusted for age, sex, site, and family. We observed a statistically significant (P = 5 × 10â»8) association between rs2384207 in 12q24, a region previously linked to several metabolic traits, and the fenofibrate-induced change in circulating adiponectin. Additionally, our genome-wide analysis of baseline adiponectin levels replicated the previously reported association with CDH13 and suggested novel associations with markers near the PCK1, ZBP1, TMEM18, and SCUBE1 genes. The findings from the single marker tests were corroborated in gene-based analyses. Biological pathway analyses suggested a borderline significant association between the EGF receptor signaling pathway and baseline adiponectin levels. CONCLUSIONS: We present preliminary evidence linking several biologically relevant genetic variants to adiponectin levels at baseline and in response to fenofibrate therapy. Our findings provide support for fine-mapping of the 12q24 region to investigate the shared biological mechanisms underlying levels of circulating adiponectin and susceptibility to metabolic disease.
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Adiponectina/sangre , Cadherinas/genética , Cromosomas Humanos Par 12 , Resistencia a Medicamentos , Fenofibrato/farmacología , Hipolipemiantes/farmacología , Polimorfismo de Nucleótido Simple , Adiponectina/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Tejido Adiposo Blanco/metabolismo , Adulto , Cadherinas/metabolismo , Femenino , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Minnesota , Análisis de Secuencia por Matrices de Oligonucleótidos , Hermanos , UtahRESUMEN
Genetic variation in fatty acid desaturases (FADS) has previously been linked to long-chain polyunsaturated fatty acids (PUFAs) in adipose tissue and cardiovascular risk. The goal of our study was to test associations between six common FADS polymorphisms (rs174556, rs3834458, rs174570, rs2524299, rs174589, rs174627), intermediate cardiovascular risk factors, and non-fatal myocardial infarction (MI) in a matched population based case-control study of Costa Rican adults (n = 1756). Generalized linear models and multiple conditional logistic regression models were used to assess the associations of interest. Analyses involving intermediate cardiovascular risk factors and MI were also conducted in two replication cohorts, The Nurses' Health Study (n = 1200) and The Health Professionals Follow-Up Study (n = 1295). In the Costa Rica Study, genetic variation in the FADS cluster was associated with a robust linear decrease in adipose gamma-linolenic, arachidonic, and eicosapentaenoic fatty acids, and significant or borderline significant increases in the eicosadienoic, eicosatrienoic, and dihomo-gamma-linolenic fatty acids. However, the associations with adipose tissue fatty acids did not translate into changes in inflammatory biomarkers, blood lipids, or the risk of MI in the discovery or the replication cohorts. In conclusion, fatty acid desaturase polymorphisms impact long-chain PUFA biosynthesis, but their overall effect on cardiovascular health likely involves multiple pathways and merits further investigation.