Association between polymorphisms in the leptin promoter and leptin receptor genes and cancer in a mediterranean population of the PREDIMED study

Mediterranean Diet Reduces the Adverse Effect of the TCF7L2-rs7903146 Polymorphism on Cardiovascular Risk Factors and Stroke Incidence

OBJECTIVE Transcription factor 7-like 2 (TCF7L2) polymorphisms are strongly associated with type 2 diabetes, but controversially with plasma lipids and cardiovascular disease. Interactions of the Mediterranean diet (MedDiet) on these associations are unknown. We investigated whether the TCF7L2-rs7903146 (C>T) polymorphism associations with type 2 diabetes, glucose, lipids, and cardiovascular disease incidence were modulated by MedDiet. RESEARCH DESIGN AND METHODS A randomized trial (two MedDiet intervention groups and a control group) with 7,018 participants in the PREvención con DIetaMEDiterránea study was undertaken and major cardiovascular events assessed. Data were analyzed at b…

Urinary Tartaric Acid, a Biomarker of Wine Intake, Correlates with Lower Total and LDL Cholesterol.

Postmenopausal women are at higher risk of developing cardiovascular diseases due to changes in lipid profile and body fat, among others. The aim of this study was to evaluate the association of urinary tartaric acid, a biomarker of wine consumption, with anthropometric (weight, waist circumference, body mass index (BMI), and waist-to-height ratio), blood pressure, and biochemical variables (blood glucose and lipid profile) that may be affected during the menopausal transition. This sub-study of the PREDIMED (Prevención con Dieta Mediterránea) trial included a sample of 230 women aged 60–80 years with high cardiovascular risk at baseline. Urine samples were diluted and filtered, and tartari…

Genome-Wide Association Study (GWAS) on Bilirubin Concentrations in Subjects with Metabolic Syndrome: Sex-Specific GWAS Analysis and Gene-Diet Interactions in a Mediterranean Population

Although, for decades, increased serum bilirubin concentrations were considered a threatening sign of underlying liver disease and had been associated with neonatal jaundice, data from recent years show that bilirubin is a powerful antioxidant and suggest that slightly increased serum bilirubin concentrations are protective against oxidative stress-related diseases, such as cardiovascular diseases. Therefore, a better understanding of the gene-diet interactions in determining serum bilirubin concentrations is needed. None of the previous genome-wide association studies (GWAS) on bilirubin concentrations has been stratified by sex. Therefore, considering the increasing interest in incorporat…

The Effect of Physical Activity and High Body Mass Index on Health-Related Quality of Life in Individuals with Metabolic Syndrome

© 2020 by the authors.

Asociaciones de la concentración de adiponectina sérica con parámetros antropométricos, bioquímicos y presión arterial en población de alto riesgo cardiovascular

Introduccion La adiponectinemia se ha asociado inversamente con obesidad abdominal, un perfil lipidico mas favorable y menor resistencia a la insulina. Sin embargo, recientes estudios en poblacion de alto riesgo cardiovascular, especialmente con funcion renal alterada, muestran que concentraciones elevadas son un indicador desfavorable. Nuestro objetivo ha sido estudiar la asociacion entre adiponectinemia y parametros antropometricos, bioquimicos y presion arterial (PA) en pacientes de alto riesgo cardiovascular. Pacientes y metodos Se estudio a 185 pacientes (133 mujeres y 52 varones), participantes del estudio PREDIMED (edad media de 65,5 ± 4,3 anos). Se obtuvieron datos clinicos, antropo…

DNA methylation of the CYP1A1 and GSTP1 genes and incidence of major cancers (lung, breast and colon) in the PREDIMED-Valencia study

MOESM1 of CLOCK gene variation is associated with incidence of type-2 diabetes and cardiovascular diseases in type-2 diabetic subjects: dietary modulation in the PREDIMED randomized trial

Additional file 1: Figure S1. Flow-chart. Figure S2. Cumulative T2D-free survival by CLOCK-rs4580704 genotypes depending on the dietary intervention group. Figure S3. Cumulative stroke-free survival by CLOCK-rs4580704 genotypes. Table S1. Characteristics of the PREDIMED study participants at baseline according to the dietary intervention groups. Table S2. Characteristics of the PREDIMED study participants at baseline according to the T2D status. Table S3. Incidence rate and hazard ratios (HR) for total cardiovascular diseases (CVD) depending on the CLOCK-rs4580704. Table S4. Incidence rate and hazard ratios (HR) for stroke depending on the CLOCK-rs4580704 in T2D subjects and stratified by d…

Global and sex-specific epigenome-wide association studies for the identification of the main methylated loci related to smoking in a mediterranean population

Abstract Background Tobacco use has been reported to be the main cause of 90% of male and 80% of female lung cancers, as well as a relevant risk factor for other cancers such as oropharynx, larynx, esophagus, stomach, liver, pancreas, kidney, bladder, and colorectum. Smoking directly affects DNA methylation and although several genes have been reported to be differentially methylated in smokers, gender differences and population-specific differences remain to be further investigated. Our aim was to undertake global and sex-specific genome-wide epigenomic studies (EWAS) in a Mediterranean population to identify the main smoking DNA-methylated genes. Methods We analyzed 88 participants in the…

Effect of an Intensive Weight-Loss Lifestyle Intervention on Kidney Function: A Randomized Controlled Trial

Introduction: Large randomized trials testing the effect of a multifactorial weight-loss lifestyle intervention including Mediterranean diet (MedDiet) on renal function are lacking. Here, we evaluated the 1-year efficacy of an intensive weight-loss intervention with an energy-reduced MedDiet (erMedDiet) plus increased physical activity (PA) on renal function. Methods: Randomized controlled "PREvención con DIeta MEDiterránea-Plus"(PREDIMED-Plus) trial is conducted in 23 Spanish centers comprising 208 primary care clinics. Overweight/obese (n = 6,719) adults aged 55-75 years with metabolic syndrome were randomly assigned (1:1) to an intensive weight-loss lifestyle intervention with an erMedDi…

Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to the Mediterranean diet pattern is low

Background: Although the Fat Mass and Obesity (FTO) and Melanocortin-4 Receptor (MC4R) genes have been consistently associated with obesity risk, the association between the obesity-risk alleles with type 2 diabetes is still controversial. In some recent meta-analyses in which significant results have been reported, the associations disappeared after adjustment for body mass index (BMI). However gene-diet interactions with dietary patterns have not been investigated. Our main aim was to analyze whether these associations are modulated by the level of adherence to the Mediterranean Diet (MedDiet). Methods: Case-control study in 7,052 high cardiovascular risk subjects (3,430 type 2 diabetes c…

Candidate Gene and Genome-Wide Association Studies for Circulating Leptin Levels Reveal Population and Sex-Specific Associations in High Cardiovascular Risk Mediterranean Subjects

Leptin is a hormone crucial in the regulation of food intake and body-weight maintenance. However, the genes and gene variants that influence its plasma levels are still not well known. Results of studies investigating polymorphisms in candidate genes have been inconsistent, and, in addition, very few genome-wide association studies (GWAS) have been undertaken. Our aim was to investigate the genes and gene variants most associated with plasma leptin concentrations in a high-cardiovascular-risk Mediterranean population. We measured plasma leptin in 1011 men and women, and analyzed the genetic factors associated using three approaches: (1) Analyzing the single nucleotide polymorphisms (SNPs) …

Abstract MP04: Taste Perception Profiles Are Associated With Patterns Of Adherence To A Mediterranean Diet Among Older Adults With Metabolic Syndrome

Objective: Evidence suggests perception of sweet, salt, sour, bitter, and umami tastes may be independently related to food preferences and intake. Our objective was to determine whether a collective measure of taste perception for all 5 tastes—“taste perception profiles”—was related to adherence to a Mediterranean diet (MedD). Methods: Participants were 367 older adults (55-75 years; 55% female) with metabolic syndrome from PREDIMED-Plus, Valencia. A data-driven clustering approach identified six taste perception profiles from baseline taste perception scores: Low All ( n = 85), High Bitter ( n = 41), High Umami ( n = 61), Low Bitter & Umami ( n = 59), High All But Bitter ( n = 72) an…

A Multi-Locus Genetic Risk Score for Primary Open-Angle Glaucoma (POAG) Variants Is Associated with POAG Risk in a Mediterranean Population: Inverse Correlations with Plasma Vitamin C and E Concentrations

Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. The genetics of POAG are complex, and population-specific effects have been reported. Although many polymorphisms associated with POAG risk have been reported, few studies have analyzed their additive effects. We investigated, in a southern European Mediterranean population, the association between relevant POAG polymorphisms, identified by initial genome-wide association studies (GWASs) and POAG risk, both separately and as an aggregated multi-locus genetic risk score (GRS). Also, bearing in mind that oxidative stress is a factor increasingly recognized in the pathogenesis of POAG, we analyzed the potential assoc…

Genetic polymorphism related to exfoliative glaucoma is also associated with primary open-angle glaucoma risk

Background To investigate the possible association of the rs2165241 polymorphism (C > T) in LOXL1 gene with the risk of primary open-angle glaucoma in a Mediterranean population. Methods The analysis of genetic polymorphisms was performed by standard TaqMan allelic discrimination technique, using a 7900HT Sequence Detection System (Applied Biosystems). Results In a recessive genetic model, the T allele of the rs2165241 polymorphism was significantly associated with the risk of primary open-angle glaucoma (TT vs. CC: odds ratios = 2.19, 95% confidence interval = [1.33–3.62]). After multivariate logistic regression model adjusted by age and weight, the magnitude of the association decreased b…

CLOCK gene variation is associated with incidence of type‑2 diabetes and cardiovascular diseases in type‑2 diabetic subjects: dietary modulation in the PREDIMED randomized trial

Background: Circadian rhythms regulate key biological processes influencing metabolic pathways. Disregulation is associated with type 2 diabetes (T2D) and cardiovascular diseases (CVD). Circadian rhythms are generated by a transcriptional autoregulatory feedback loop involving core clock genes. CLOCK (circadian locomotor output cycles protein kaput), one of those core genes, is known to regulate glucose metabolism in rodent models. Cross-sectional studies in humans have reported associations between this locus and obesity, plasma glucose, hypertension and T2D prevalence, supporting its role in cardiovascular risk. However, no longitudinal study has investigated the association between CLOCK…

Legume consumption is inversely associated with type 2 diabetes incidence in adults: A prospective assessment from the PREDIMED study

Background & aims: Legumes, a low-energy, nutrient-dense and low glycemic index food, have shown beneficial effects on glycemic control and adiposity. As such, legumes are widely recommended in diabetic diets, even though there is little evidence that their consumption protects against type 2 diabetes. Therefore the aim of the present study was to examine the associations between consumption of total legumes and specific subtypes, and type 2 diabetes risk. We also investigated the effect of theoretically substituting legumes for other protein- or carbohydrate-rich foods. Methods: Prospective assessment of 3349 participants in the PREvención con DIeta MEDiterránea (PREDIMED) study without ty…

Chronological Age Interacts with the Circadian Melatonin Receptor 1B Gene Variation, Determining Fasting Glucose Concentrations in Mediterranean Populations. Additional Analyses on Type-2 Diabetes Risk

Gene-age interactions have not been systematically investigated on metabolic phenotypes and this modulation will be key for a better understanding of the temporal regulation in nutrigenomics. Taking into account that aging is typically associated with both impairment of the circadian system and a decrease in melatonin secretion, we focused on the melatonin receptor 1B (MTNR1B)-rs10830963 C&gt

Effect of the polymorphism rs2066844 of the NOD2 gene on colon cancer incidence in a high cardiovascular risk population: Modulation by gender

Association of the rs4988235 in the lactase gene with obesity and its modulation by dairy products in a Mediterranean population

The -13910C>T polymorphism (rs4988235) upstream from the lactase (LCT) gene, strongly associated with lactase persistence (LP) in Europeans, is emerging as a new candidate for obesity. We aimed to analyze the association of this polymorphism with obesity-related variables and its modulation by dairy product intake in an elderly population. We studied 940 high-cardiovascular risk Spanish subjects (aged 67 ± 7 years). Dairy product consumption was assessed by a validated questionnaire. Anthropometric variables were directly measured, and metabolic syndrome-related variables were obtained. Prevalence of genotypes was: 38.0% CC (lactase nonpersistent (LNP)), 45.7% CT, and 16.3% TT. The CC genot…

Seafood Consumption, Omega-3 Fatty Acids Intake, and Life-Time Prevalence of Depression in the PREDIMED-Plus Trial.

Background: The aim of this analysis was to ascertain the type of relationship between fish and seafood consumption, omega-3 polyunsaturated fatty acids (&omega

Milk and Dairy Products Intake Is Related to Cognitive Impairment at Baseline in Predimed Plus Trial

Scope: To examine the association between milk and dairy products intake and the prevalence of cognitive decline among Spanish individuals at high cardiovascular risk. Methods and results: Cross-sectional analyses are performed on baseline data from 6744 adults (aged 55-75 years old). Intake of milk and dairy products is estimated using a food frequency questionnaire grouped into quartiles. The risk of developing cognitive impairment is based on the Mini-Mental State Examination (MMSE). A higher prevalence of cognitive decline was found in subjects who consumed more grams. Patients with worse MMSE score (10-24) consumed a mean of 395.14 ± 12.21 g, while patients with better MMSE score (27-3…

Polyphenol intake and cardiovascular risk in the PREDIMED-Plus trial. A comparison of different risk equations

Abstract Introduction and objectives Quantification of cardiovascular risk has been based on scores such as Framingham, Framingham-REGICOR, SCORE or Life's Simple 7 (LS7). In vitro, animal, and randomized clinical studies have shown that polyphenols may provide benefits to the vascular system and reduce the inflammatory response. However, some clinical-epidemiological studies have yielded inconsistent results. Our aim was to assess the possible association between intake of the various polyphenol classes and established cardiovascular scores. Methods This cross-sectional analysis involved 6633 PREDIMED-Plus study participants. Food polyphenol content was estimated by a semiquantitative food…

Association of the rs4567312 variant in the leptin receptor gene with plasma leptin concentrations and lung cancer incidence in the PREDIMED study

The rs9939609-fto polymorphism is associated with methylation levels in both men and women from a high cardiovascular risk population

Adherence to the mediterranean diet modulates the association between the abca1 gene, plasma lipids and diabetes in a high-risk population

Effect of the polymorphisms rs1476413, rs1801131, rs4846052 and rs6541003 of the MTHFR gene on prostate cancer in a high cardiovascular risk population

Association Between Lifestyle and Hypertriglyceridemic Waist Phenotype in the PREDIMED-Plus Study.

Objective: The hypertriglyceridemic waist (HTGW) phenotype is characterized by abdominal obesity and high levels of triglycerides. In a cross-sectional assessment of PREDIMED-Plus trial participants at baseline, HTGW phenotype prevalence was evaluated, associated risk factors were analyzed, and the lifestyle of individuals with metabolic syndrome and HTGW was examined. Methods: A total of 6,874 individuals aged 55 to 75 with BMI ≥ 27 and < 40 kg/m2 were included and classified by presence (HTGW+ ) or absence (HTGW- ) of HTGW (waist circumference: men ≥ 102 cm, women ≥ 88 cm; fasting plasma triglycerides ≥ 150 mg/dL). Analytical parameters and lifestyle (energy intake and expenditure) were a…

Association between taste perception and adiposity in overweight or obese older subjects with metabolic syndrome and identification of novel taste-related genes.

BACKGROUND The relation between taste perception, diet, and adiposity remains controversial. Additionally, there is a lack of knowledge on the polymorphisms influencing taste given the scarcity of genome-wide association studies (GWASs) published. OBJECTIVES We studied the relation between perception of the basic tastes, i.e., sweet, salty, bitter, sour, and umami (separately and jointly in a "taste score"), and anthropometric measurements in older subjects with metabolic syndrome (MetS). GWASs were undertaken to identify genes associated with basic tastes and their score. METHODS Taste perception was cross-sectionally determined by challenging subjects (381 older individuals with MetS) wit…

Gene-environment interactions of CETP gene variation in a high cardiovascular risk Mediterranean population

Genome-wide association studies show that cholesteryl ester transfer protein (CETP) single nucleotide polymorphisms (SNPs) are more strongly associated with HDL cholesterol (HDL-C) concentrations than any other loci across the genome. However, gene-environment interactions for clinical applications are still largely unknown. We studied gene-environment interactions between CETP SNPs and dietary fat intake, adherence to the Mediterranean diet, alcohol consumption, smoking, obesity, and diabetes on HDL-C in 4,210 high cardiovascular risk subjects from a Mediterranean population. We focused on the −4,502C>T and the TaqIB SNPs in partial linkage disequilibrium (D'= 0.88; P < 0.001). They were i…

Bitter, Sweet, Salty, Sour and Umami Taste Perception Decreases with Age: Sex-Specific Analysis, Modulation by Genetic Variants and Taste-Preference Associations in 18 to 80 Year-Old Subjects

There is growing interest in relating taste perception to diet and healthy aging. However, there is still limited information on the influence of age, sex and genetics on taste acuity as well as on the relationship between taste perception and taste preferences. We have analysed the influence of age on the intensity rating of the five basic tastes: sweet, salty, bitter, sour and umami (separately and jointly in a &ldquo

Education modulates the association of the FTO rs9939609 polymorphism with body mass index and obesity risk in the Mediterranean population

Objective To define whether the rs9939609 FTO (fat mass and obesity associated) single nucleotide polymorphism (SNP) is associated with anthropometric measurements and its modulation by educational level in a Mediterranean population. Methods We studied 3 independent adult samples: a random sample (n = 1580) from the general population (GP), obese hospital patients (OHP) (n = 203) and elderly subjects (n = 1027) with high cardiovascular risk (HCR). Weight and height were directly measured. Education and physical activity (PA) were measured using questionnaires. Results The rs9939609 presented heterogeneous associations with BMI. In the GP, the minor A-allele was significantly associated wit…

Ultra-Performance Liquid Chromatography-Ion Mobility Separation-Quadruple Time-of-Flight MS (UHPLC-IMS-QTOF MS) Metabolomics for Short-Term Biomarker Discovery of Orange Intake: A Randomized, Controlled Crossover Study

A major problem with dietary assessments is their subjective nature. Untargeted metabolomics and new technologies can shed light on this issue and provide a more complete picture of dietary intake by measuring the profile of metabolites in biological samples. Oranges are one of the most consumed fruits in the world, and therefore one of the most studied for their properties. The aim of this work was the application of untargeted metabolomics approach with the novel combination of ion mobility separation coupled to high resolution mass spectrometry (IMS-HRMS) and study the advantages that this technique can bring to the area of dietary biomarker discovery, with the specific case of biomarker…

Statistical and biological gene-lifestyle interactions of MC4R and FTO with diet and physical activity on obesity: new effects on alcohol consumption

Background: Fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) and are relevant genes associated with obesity. This could be through food intake, but results are contradictory. Modulation by diet or other lifestyle factors is also not well understood. Objective: To investigate whether MC4R and FTO associations with body-weight are modulated by diet and physical activity (PA), and to study their association with alcohol and food intake. Methods: Adherence to Mediterranean diet (AdMedDiet) and physical activity (PA) were assessed by validated questionnaires in 7,052 high cardiovascular risk subjects. MC4R rs17782313 and FTO rs9939609 were determined. Independent and joint associati…

Common cholesteryl ester transfer protein gene variation related to high-density lipoprotein cholesterol is not associated with decreased coronary heart disease risk after a 10-year follow-up in a Mediterranean cohort: Modulation by alcohol consumption.

Despite the consistent association between cholesteryl ester transfer protein (CETP) gene variation and plasma HDL-C, huge controversy still rages on its association with coronary heart disease (CHD). We investigated the association between the CETP-TaqIB polymorphism, HDL-C and incident CHD in a Mediterranean population.A nested case-control study among participants of the Spanish EPIC cohort was performed. 41,440 healthy individuals (30-69 years) were followed up over a 10-year period, incident CHD cases being identified. We analyzed 557 confirmed CHD cases and 1180 healthy controls.Despite B2B2 subjects having the highest HDL-C concentrations and B1B1, the lowest (P0.001), no protective …

Influence of Demographic and Lifestyle Variables on Plasma Magnesium Concentrations and Their Associations with Cardiovascular Risk Factors in a Mediterranean Population.

Several studies have shown that a low magnesium (Mg) intake in the diet is associated with greater cardiovascular risk and greater risk of diabetes. However, the results are not consistent in all populations. To minimize the biases derived from diet measurement, more objective biomarkers of magnesium status have been proposed. Although there is still no ideal biomarker for Mg, several studies have shown that plasma Mg concentrations could be a relatively acceptable biomarker for cardiovascular risk assessment. However, further studies are required to better characterize this marker in different populations. Our aim was to analyze the association between plasma Mg concentrations (measured th…

Transcriptomic autophagy-related gene signature investigation for type 2 diabetes in Mediterranean subjects

Abstract Background Autophagy (involving degradation and clearance of damaged organelles and compounds) plays a role in type 2 diabetes (T2D). There are three main types of autophagy and several genes involved. These genes have been well studied in animal models, but there are few transcriptomic studies in humans. Our aim is to analyze the differential gene expression, and the functional enrichment of the main autophagy-related genes (ARG) in T2D subjects from a Mediterranean population Methods We analyzed 120 White-European subjects (mean age 61,4 years; 50% women; 24 T2D) from Valencia, Spain. Clinical and lifestyle data were obtained. ARN was isolated from blood. Transcriptome-wide gene …

Dietary inflammatory index and all-cause mortality in large cohorts: The SUN and PREDIMED studies

[Background]: Inflammation is known to be related to the leading causes of death including cardiovascular disease, several types of cancer, obesity, type 2 diabetes, depression-suicide and other chronic diseases. In the context of whole dietary patterns, the Dietary Inflammatory Index (DII®) was developed to appraise the inflammatory potential of the diet. [Objective]: We prospectively assessed the association between DII scores and all-cause mortality in two large Spanish cohorts and valuated the consistency of findings across these two cohorts and results published based on other cohorts.

Genome-Wide Association Study for Serum Omega-3 and Omega-6 Polyunsaturated Fatty Acids: Exploratory Analysis of the Sex-Specific Effects and Dietary Modulation in Mediterranean Subjects with Metabolic Syndrome.

Many early studies presented beneficial effects of polyunsaturated fatty acids (PUFA) on cardiovascular risk factors and disease. However, results from recent meta-analyses indicate that this effect would be very low or nil. One of the factors that may contribute to the inconsistency of the results is that, in most studies, genetic factors have not been taken into consideration. It is known that fatty acid desaturase (FADS) gene cluster in chromosome 11 is a very important determinant of plasma PUFA, and that the prevalence of the single nucleotide polymorphisms (SNPs) varies greatly between populations and may constitute a bias in meta-analyses. Previous genome-wide association studies (GW…