Mild cognitive impairment has been associated with several genetic and lifestyle factors including diet. However, the number of transcriptome-wide association studies (TWAS) in this field is still ...very scarce. Our aim was to carry out a TWAS adjusted for adherence to Mediterranean diet (MedDiet) to identify the differentially expressed genes associated with a global cognitive function score, tacking diet into account.
A set of cognitive functions related to cognitive decline was assessed in 103 subjects (aged 64.8 years) with metabolic syndrome. A principal component analysis (PCA) on 5 variables including semantic and verbal fluency, the trail making test (TMT) A and B and the digits total test, was performed to reduce multidimensionality. Only one component with eigenvalues >1 was identified. This latent variable had strong direct correlations with semantic and verbal fluency and the digits test, and negative with TMT-A and TMT-B. The standardized score was used as the global cognitive variable representing attention and executive functions. RNA was isolated from leukocytes and after quality control, using the Affymetrix human 20 array, a TWAS was undertaken according to the quality control procedures.
In the TWAS adjusted for sex, age, batch effect, leukocyte types, body mass index, smoking, medications and adherence to MedDiet, we identified several top-ranked differentially expressed genes associated with the global cognitive score, including: HBD3 (Methyl-cpg Binding Domain protein 3) gene (p = 8.9 × 10−6) as the hit, previously associated with neuropathy; GABRP (Gamma-Aminobutyric Acid Type A receptor Pi), involved in the synaptic transmission; and LAG3 (Lymphocyte activating 3), related to neuroinflammation, among others. Moreover, MedDiet was significantly related to the expression of LAG3 gene.
In this TWAS, a composite score for cognitive function is associated with differential expression of several genes related with neurotransmission and neuroinflammation in leukocytes, some of them being additionally modulated by adherence to MedDiet.
Generalitat Valenciana (grant PROMETEO/2021/021). Grant PID2019-108858RB-I00 is funded by AEI 10.13039/501,100,011,033 and, by “ERDF A way of making Europe”.
Autophagy is a dynamic process responsible for protein degradation/recycling as a protective mechanism in response to stress and inflammation. Its deregulation has been associated with common cv and ...brain diseases. In animal models, autophagy activity is regulated by epigenetic mechanisms in response to diet. However, very few studies have analyzed the diet-autophagy relationship in humans. Our aim is to study the association between the adherence to the Mediterranean diet (MedDiet) and the DNA-methylation of the main autophagy-related genes.
We have analyzed 410 subjects (aged 65.5 y) with metabolic syndrome from Valencia (Spain) and measured the adherence to the MedDiet by a 17-item score. DNA methylation from leukocytes was analyzed by the Illumina EPIC850K Human array. A comprehensive list (n = 141) of the main autophagy-related genes was selected from the literature. Multivariate adjusted models including potential confounders were fitted and gene-ontology (GO) enrichment was analyzed.
In a model adjusted for sex, age, batch effect, diabetes, body mass index, medications, leukocyte types, smoking and adherence to MedDiet, we found significant associations between MedDiet adherence and the differential methylation of several cpg sites of the selected autophagy-related genes: cg17676428 (top-ranked cpg site) in TOLLIP (Toll interactive protein) gene (p = 9.3 × 10–6). This is a ubiquitin binding protein that regulates innate immune response. Its deficiency alters atherosclerosis and steatosis. The other hits: cg12573747 in HTT (Huntingtin) gene (p = 4.5 × 10–5), a gene related to the DNA protection in neurons; the cg09197074 (p = 7.8 × 10–5) in HSPA8 (Heat shock protein family A (Hsp70) member 8), that functions as a chaperone and protects the proteome from stress. The GO analysis identified as top-ranked enriched functions: autophagosome membrane; organelle disassembly; selective autophagy; vacuole; phagophore assembly; etc.
A higher adherence to the MedDiet is associated with differential DNA-methylation on relevant autophagy related genes and may have a potential effect upregulating autophagy.
Generalitat Valenciana (grant PROMETEO/2021/021). Grant PID2019-108858RB-I00 is funded by AEI 10.13039/501100011033 and, by “ERDF A way of making Europe”.
Resumen Tanto la nutrigenética como la nutrigenómica son disciplinas dentro de la denominada genómica nutricional, que, en sentido amplio, proporciona el marco de integración de las distintas ómicas ...con las ciencias de la alimentación y nutrición. Tras décadas de estudios nutrigenéticos y nutrigenómicos, se dispone de una cantidad relevante de conocimientos para plantear su aplicación en la denominada nutrición de precisión. Esta nueva disciplina plantea que hay que tener en cuenta las características particulares de la persona para proporcionar la mejor dieta para prevenir o tratar la enfermedad. Los marcadores ómicos se consideran relevantes en dicha personalización. Existen muchos alimentos, nutrientes y patrones de dieta que se han investigado en nutrigenética y nutrigenómica; entre ellos, podemos mencionar el patrón de dieta mediterránea. A pesar de la heterogeneidad en la definición de dieta mediterránea, existen varios estudios que muestran que la dieta mediterránea puede interaccionar con el genoma, disminuyendo el riesgo de enfermedad en las personas genéticamente más susceptibles. Paralelamente, algunos estudios están mostrando los mecanismos por los que la dieta mediterránea puede ejercer este efecto protector. Conocer con más detalle la susceptibilidad genética, los mecanismos epigenéticos, la influencia del metaboloma y de otras ómicas puede ser relevante en gastronomía, entendida como la práctica del arte de elegir, cocinar y comer los alimentos. Esta influencia ómica no solo podemos encontrarla en los fenotipos de salud-enfermedad, sino también en la percepción del sabor y del olor de los alimentos (las preferencias por determinadas comidas). Todo ello, bien integrado, puede contribuir al incremento del disfrute a la vez que se sigue una alimentación saludable.
This study cross-sectionally examines in the elderly population: (a) the association of type 2 diabetes with executive function (EF); (b) the effect of BMI on both type 2 diabetes and EF; (c) the ...association between glycaemia control and EF in type 2 diabetes. 6823 older individuals with overweight/obesity and metabolic syndrome participating in the PREDIMED-PLUS study, were assessed with a battery of cognitive tests and a medical interview. ANOVA showed a significantly worse performance on EF in type 2 diabetes vs. non-diabetic individuals. Two complementary models were displayed: (1) in the whole sample, the presence of type 2 diabetes, depressive symptoms and BMI had a direct negative effect on EF, while apnoea had an indirect negative effect; (2) in the diabetes subsample, higher illness duration was associated with worse performance in EF. Participants with type 2 diabetes and HbA1c<53 mmol/mol displayed better cognitive performance when compared to those with HbA1c≥53 mmol/mol. Our results provide a controlled comprehensive model that integrates relevant neuropsychological and physical variables in type 2 diabetes. The model suggests that, to improve treatment adherence and quality of life once diabetes has been diagnosed, cognitive decline prevention strategies need to be implemented while monitoring depressive symptoms, BMI and glycaemia control.
To investigate the association between taste perception for sweet, salt, sour, bitter and umami and food category intakes. We hypothesized that greater taste perception will be inversely associated ...with the amount consumed.
A cross-sectional baseline analysis was performed on community-dwelling overweight adults with metabolic syndrome (N = 367, 55–75y) from the PREDIMED-PLUS Trial, University of Valencia Center, Spain. Taste perception was determined by challenging subjects with standard solutions of sweet, salt, sour, bitter and umami (400 mM sucrose, 200 mM NaCl, 34 mM citric acid, 5.6 mM phenylthiocarbamide (PTC), 200 mM monopotassium glutamate, respectively) and evaluated on a 0–5 scale. Outcomes included intake (servings/week) of food categories derived from a validated food frequency questionnaire: fruit (citrus/non-citrus/nuts), vegetables (cruciferous/non-cruciferous), protein (eggs/fishfresh/shell/canned/meatprocessed/unprocessed), grains (legumes/refined/whole), dairy (regular/low- & no-fat) and oils (extra virgin olive (EVOO)/olive/vegetable). Multivariable linear regression models were used to assess associations of perception for each taste and consumption of each food category (untransformed or transformed, for normality).
After controlling for age, sex, diabetes, smoking, physical activity and energy intake, sweet was inversely associated with vegetables (β = −1.1; 95% CI = −2.0, −0.2), particularly non-cruciferous (β = −1.0; P = 0.02), and citrus fruit (β = −0.5; P < 0.01); salt was positively associated with fruit (β = 1.0; 95% CI = 0.04, 1.9), particularly non-citrus (β = 0.6; P = 0.03), and olive oil (β = 1.1; P = 0.02) but negatively associated with EVOO (β = −1.4; P = 0.02); sour was positively associated with cruciferous vegetables (β = 0.1; P = 0.04); bitter was inversely associated with canned fish (β = −0.1; P = 0.03); and umami was positively associated with non-cruciferous vegetables (β = 0.7; P = 0.04) and inversely associated with regular dairy (β = −0.4; P = 0.04).
Our hypothesis was rejected. Taste perception for sweet, salt, sour, bitter and umami differentially affected intake of various food categories; suggesting a role of taste perception in diet quality, energy balance and diet-related chronic diseases.
This study was funded by the ARS/USDA, and the Spanish Ministry of Health (Instituto de Salud Carlos III), SAF2016–80,532-R, and the Generalitat Valenciana.
Resumen Tanto la nutrigenética como la nutrigenómica son disciplinas dentro de la denominada genómica nutricional, que, en sentido amplio, proporciona el marco de integración de las distintas ómicas ...con las ciencias de la alimentación y nutrición. Tras décadas de estudios nutrigenéticos y nutrigenómicos, se dispone de una cantidad relevante de conocimientos para plantear su aplicación en la denominada nutrición de precisión. Esta nueva disciplina plantea que hay que tener en cuenta las características particulares de la persona para proporcionar la mejor dieta para prevenir o tratar la enfermedad. Los marcadores ómicos se consideran relevantes en dicha personalización. Existen muchos alimentos, nutrientes y patrones de dieta que se han investigado en nutrigenética y nutrigenómica; entre ellos, podemos mencionar el patrón de dieta mediterránea. A pesar de la heterogeneidad en la definición de dieta mediterránea, existen varios estudios que muestran que la dieta mediterránea puede interaccionar con el genoma, disminuyendo el riesgo de enfermedad en las personas genéticamente más susceptibles. Paralelamente, algunos estudios están mostrando los mecanismos por los que la dieta mediterránea puede ejercer este efecto protector. Conocer con más detalle la susceptibilidad genética, los mecanismos epigenéticos, la influencia del metaboloma y de otras ómicas puede ser relevante en gastronomía, entendida como la práctica del arte de elegir, cocinar y comer los alimentos. Esta influencia ómica no solo podemos encontrarla en los fenotipos de salud-enfermedad, sino también en la percepción del sabor y del olor de los alimentos (las preferencias por determinadas comidas). Todo ello, bien integrado, puede contribuir al incremento del disfrute a la vez que se sigue una alimentación saludable.
Resumen Introducción: aunque la obesidad es un problema de salud multidimensional, pocos estudios de investigación cualitativa han analizado el discurso de personas obesas con perspectiva de género ...para conocer con mayor profundidad información difícilmente obtenible con técnicas cuantitativas. Objetivo: analizar el discurso de personas obesas mediante grupos de discusión en cuanto a factores que subyacen en la obesidad, percepción del riesgo de patologías, pérdida peso y otros factores relevantes. Métodos: se realizaron dos grupos de discusión en sesiones separadas, homogéneos por sexo, con un total de 14 participantes. Un moderador dirigió la sesión contemplando las distintas dimensiones del problema. Los grupos fueron grabados en audio y transcritos textualmente. Se analizó el discurso por métodos cualitativos. Resultados: se observaron importantes diferencias en la perspectiva entre hombres y mujeres. Las causas autopercibidas de obesidad para las mujeres fueron el embarazo y el periodo menopáusico. Los hombres la atribuyeron a los hábitos alimenticios y costumbres culturales. Para los hombres la finalidad de disminuir el peso era mejorar su salud, sin embargo, las mujeres incluían también la estética. Ambos sexos pensaban que la obesidad puede acarrear grandes problemas. Ellas revelaron tener miedo a engordar, mientras que los hombres no lo expusieron. También se observaron diferencias en las estrategias de lucha contra la obesidad. Conclusiones: las diferencias en la percepción de las causas y el abordaje de la obesidad entre hombres y mujeres nos indican la necesidad de considerar las medidas preventivas y terapéuticas teniendo en cuenta el sexo, así como aspectos ambientales que envuelven al paciente.
El índice tobillo-brazo (ITB) es un indicador de enfermedad arterial periférica (EAP). El objetivo de este estudio es evaluar la asociación entre la EAP medida con el ITB y el rendimiento cognitivo ...de individuos con sobrepeso u obesidad y síndrome metabólico.
Estudio transversal realizado con los datos basales del estudio PREDIMED-Plus, en el que se incluyó a un total de 4.898 participantes (tras excluir a aquellos sin medición de ITB) de entre 55 y 75 años, con sobrepeso u obesidad y síndrome metabólico. En la visita basal se midió el ITB según un protocolo estandarizado, así como otros factores de riesgo cardiovascular (diabetes mellitus, dislipemia e hipertensión arterial, entre otros). Para la evaluación del rendimiento cognitivo, se aplicaron diferentes pruebas validadas en población española (Mini-mental Test, test de fluencia verbal semántica y fonológica, test de valoración de memoria de trabajo, test del trazo y test del reloj). Para evaluar la asociación entre el ITB y el rendimiento cognitivo, se utilizaron modelos lineales generalizados.
El 3,4% de los participantes tenían EAP, definida por un ITB ≤ 0,9, y un 3,3%, calcificación arterial definida por un ITB ≥ 1,4. La EAP se asoció con la edad, la presión arterial sistólica y los indicadores de obesidad, mientras que la calcificación arterial se asoció también con obesidad y diabetes. Entre el rendimiento cognitivo y el ITB o la EAP, no se observaron asociaciones significativas.
En nuestra muestra la EAP aumenta con la edad, la presión arterial y los indicadores de obesidad. No se observa una asociación significativa entre el ITB, la EAP y el rendimiento cognitivo.
The ankle-brachial index (ABI) is an indicator of peripheral artery disease (PAD). The aim of this study was to assess the association between PAD, measured with the ABI, and cognitive function in persons with overweight or obesity and metabolic syndrome.
Cross-sectional study conducted with baseline data from the PREDIMED-Plus study, which included 4898 participants (after exclusion of those without ABI measurements) aged between 55 and 75 years, and with overweight or obesity and metabolic syndrome. At the baseline assessment, we measured the ABI with a standardized protocol and assessed the presence of other cardiovascular risk factors (eg, diabetes, dyslipidemia, hypertension). Cognitive function was evaluated using several tests validated for the Spanish population (mini-mental state examination MMSE, phonological and semantic verbal fluency test, WAIS-III working memory index WMI, parts A and B of the trail making test (TMT), and clock drawing test). Generalized linear models were used to assess the association between the ABI and cognitive function.
Among the participants, 3.4% had PAD defined as ABI ≤ 0.9, and 3.3% had arterial calcification defined as ABI ≥ 1.4. PAD was associated with age, systolic blood pressure and obesity indicators, while arterial calcification was also associated with obesity and diabetes. No significant associations were observed between cognitive function and ABI or PAD.
In our sample, the presence of PAD increased with age, blood pressure, and obesity. No significant association was observed between ABI, PAD, or cognitive function.
Glycine is a novel circulating marker for metabolic diseases associated with lower type-2 diabetes and protection against obesity in some studies. Circulating glycine levels are genetically ...determined under the control of several loci. The locus most strongly associated is the carbamoyl-phosphate synthase I (CPS1). Interestingly, some sex-specific genome-wide association studies (GWAS) showed differences in the effect of the main single nucleotide polymorphisms (SNPs) in this locus on glycine levels (significant sex * CPS1 interactions). However, the potential mechanisms explaining this sex-heterogeneity are unknown. Therefore, our aims were: 1) to analyze whether the sex * CPS1 interaction for serum glycine is present in subjects from a Mediterranean population, and 2) to test, in another population, the glycine sex-specific associations with obesity, using a Mendelian randomization approach.
We studied 426 subjects (aged 55–75 y) with metabolic syndrome from the PREDIMED Plus-Valencia Study. Serum glycine was determined by NMR spectroscopy. We screened the CPS1 gene for SNP associations. In another Mediterranean population (PREDIMED-Valencia participants, n = 1009) we analyzed the sex-specific associations between the genetically determined glycine (CPS1-SNP) and obesity, using Mendelian randomization.
In the PREDIMED Plus-Valencia subjects, serum glycine levels were higher in women than in men (280 vs 240 micromol/L, respectively; P = 1.4 × 1E15). The CPS1-rs7684 (3’-UTR) SNPs was strongly associated with glycine levels in women but not in men (P for sex * CPS1 interaction = 0.004), replicating previous findings. The minor allele was associated with lower serum glycine. In the Mendelian randomization study in the population with unmeasured glycine levels, the CPS1-rs7684 SNPs presented a sex-specific interaction for obesity (P < 0.05). Women with the minor allele (lower glycine levels) were more likely to be obese than homozygous women for the major allele (P < 0.05). No associations were detected in men.
We replicated the sex * CPS1 interaction in determining glycine levels and also detected sex * CPS1 interactions for obesity risk.
Generalitat Valenciana (PROMETEO2017/017, APOSTD/2019/136), Fundació La Marató de TV3 (538/U/2016), and CIBEROBN.
Understanding individual-level drivers of food intake is critical when personalizing dietary guidance. One likely driver is taste perception; yet, limited data relate perception of all 5 tastes ...(sweet, salt, sour, bitter, umami) to dietary patterns (DPs). Our aim was to determine whether a multivariable measure of taste perception, taste perception profiles, was associated with adherence to empirically derived DPs.
Participants were 367 community-dwelling adults with metabolic syndrome from PREDIMED-Plus, Valencia (55–75 years; 55% female). Six taste perception profiles were derived from 5 taste perception scores via a data-driven clustering approach: Low All (23%), High Bitter (16%), High Umami (17%), Low Bitter & Umami (20%), High All But Bitter (13%) and High All But Umami (11%). DPs were derived via principal component analysis using food groupings tabulated from food frequency questionnaires. Generalized linear models were used to examine relations between taste perception profiles and DP adherence, adjusting for confounders.
Three DPs were identified, explaining 25% of total variance: a high fruit, vegetable and whole grain DP (Fruit/Veg), a high fat, sugar and refined grain DP (Fat/Sug) and a high alcohol, salt and processed meat DP (Alch/Salt). Adherence to the DPs differed by profile. Across all profiles, High Bitter and Low All individuals were most likely to follow the Alch/Salt DP (44% and 39% in highest tertial of adherence, respectively; P = 0.03), while those with High All But Bitter and High Umami tended to follow the Fat/Sug DP (42% and 39% in highest tertial, respectively; P = 0.08). Compared to Low All individuals, after adjusting for age, sex, physical activity, diabetes and BMI, those with Low Bitter & Umami adhered less to the Alch/Salt DP (β 95% CI = –0.3 –0.6, –0.03) while those with High Umami adhered more to the Fat/Sug DP (0.4 0.1, 0.8).
Among older adults with metabolic syndrome, taste perception profiles were differentially associated with adherence to empirically derived DPs, suggesting the benefit of using taste perception profiles when customizing risk reduction dietary guidance.
ARS/USDA, HNRCA Cassidy Student Research Award, Spanish Ministry of Health (Instituto de Salud Carlos III; SAF2016–80532-R), CIBEROBN (06/03/0035) and Generalitat Valenciana (PROMETEO 17/2017).
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