Abstract only
Introduction:
Short sleep duration is associated with increased cardiometabolic risk. DNA methylation plays a critical role in the regulation of gene expression and studies suggest that ...sleep deprivation may alter DNA-methylation patterns. However, most findings are from acute sleep deprivation or short duration studies.
Hypothesis:
Prolonged sleep restriction study that mimics real-life situations is associated with differentially methylated CpG loci (DML) in the core clock candidate genes and across the epigenome in an epigenome-wide association study (EWAS)
Methods:
Sixty participants (65% women) aged 21-73 y were included in randomized crossover studies with 2 phases of 6 weeks each. Phases differed in sleep duration: either adequate sleep (AS; sleep ≥7h/night) or sleep restriction (SR; -1.5h/night relative to AS). DNA was isolated from whole blood at wk 0 and wk 6 of each phase. DNA methylation (DNAm) was quantified the Illumina Infinium MethylationEPIC BeadChip array v.2.0 (>900K methylation sites) and Partek Genomic Suite v.720.0831. After quality control and normalization, several global and stratified EWASs were performed to test the impact of sleep condition on DNAm. Analyses were adjusted for week, phase, sex, age, BMI and cell type composition. We also focused on methylation changes of the selected core-clock candidate genes (
RORA, CRY1, NR1D2, TIMELESS, NPAS2, NFIL3, RORB, PER3, CSNK1E, ARNTL2, CRY2, CLOCK, ARNTL, RORC, PER2, BHLHE40, NR1D1, CSNK1D, BHLHE41 and PER1
).
Results:
In the candidate gene approach, we detected several significant DML. Top-ranked DML in selected core clock genes with significant interactions between condition and time were: cg02394126 at
ARNTL
(p<0.001), cg23506964 at
CLOCK
(p=0.001), cg03701037 at
NPAS2
(p=0.009), cg06606972 at
NPAS2
(p=0.009), and cg13576304 at
RORA
(p=0.008). Hypermethylation was primarily observed after 6 wk of SR vs AS for cg02394126, cg23506964, cg03701037, and cg06606972, while hypomethylation was observed cg13576304 (
RORA
). In our EWAS, we detected some suggestive significant condition x time interactions in cg23738833 at
SNHG3-RCC1
(p=1,34E-06), cg13280380 in the
FAF1
gene (p=2,25E-05), cg03179866 in the
MMP12
gene (p=2,78E-05), and cg13063696 (p=3,21E-05). All but cg23738833 (
SNHG3-RCC1
) showed hypermethylation after 6 wk of SR vs AS.
Conclusion:
Six weeks of mild SR was associated with changes in DNAm in core-clock candidate genes and in other genes in the EWAS. However, further studies are needed to confirm these findings and determine the functional pathways.
Abstract Applications for automating the most commonly used dietary surveys in nutritional research, Food Frequency Questionnaires (FFQs) and 24 h Dietary Recalls (24HDRs), are reviewed in this ...paper. A comprehensive search of electronic databases was carried out and findings were classified by a group of experts in nutrition and computer science into: (i) Computerized Questionnaires and Web-based Questionnaires; (ii) FFQs and 24HDRs and combinations of both; and (iii) interviewer-administered or self-administered questionnaires. A discussion on the classification made and the works reported is included. Finally, works that apply innovative technologies are outlined and the future trends for automating questionnaires in nutrition are identified.
Increasingly, studies showing the protective effects of the Mediterranean diet (MedDiet) on different diseases (cardiovascular, diabetes, some cancers, and even total mortality and aging indicators) ...are being published. The scientific evidence level for each outcome is variable, and new studies are needed to better understand the molecular mechanisms whereby the MedDiet may exercise its effects. Here, we present recent advances in understanding the molecular basis of MedDiet effects, mainly focusing on cardiovascular diseases but also discussing other related diseases. There is heterogeneity in defining the MedDiet, and it can, owing to its complexity, be considered as an exposome with thousands of nutrients and phytochemicals. We review MedDiet composition and assessment as well as the latest advances in the genomic, epigenomic (DNA methylation, histone modifications, microRNAs, and other emerging regulators), transcriptomic (selected genes and whole transcriptome), and metabolomic and metagenomic aspects of the MedDiet effects (as a whole and for its most typical food components). We also present a critical review of the limitations of the studies undertaken and propose new analyses and greater bioinformatic integration to better understand the most important molecular mechanisms whereby the MedDiet as a whole, or its main food components, may exercise their protective effects.
Abstract only
Background:
Beyond taste perception, taste receptors in the mouth and gastrointestinal tract have been linked to the regulation of energy balance, endocrine function and glucose ...homeostasis. Despite this, little is known about the relationship between perception for the 5 tastes (sweet, salt, sour, bitter and umami) and diet-related chronic disease risk.
Objective:
To investigate the association between perception for the 5 tastes and diabetes status.
Methods:
A cross-sectional baseline analysis was performed on older (55-75 years), overweight (BMI, ≥27-<40) adults diagnosed with metabolic syndrome who were participating in the PREDIMED-PLUS Valencia trial (N=367). Taste perception was measured by challenging participants with standard solutions representing 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 was evaluated on a 0-5 unit scale. Diabetes status was determined by self-reported clinical diagnosis. Multivariable logistic regression models that included all 5 tastes were used to test the association between taste perception and diabetes status.
Results:
The prevalence of diabetes in this cohort was 38%. Compared to individuals without diabetes, individuals with diabetes had significantly lower bitter taste perception (unadjusted means: 1.6 versus 1.1 units, respectively) (t-test p<0.001). After adjusting for age, sex, smoking status, physical activity, BMI and medication use, a 1 unit increase in bitter taste perception was associated with a 42% lower odds of being diagnosed with diabetes (adjusted odds ratio aOR = 0.58; 95% CI = 0.38, 0.84, p<0.001). Although mean perceptions for sweet, salt, sour and umami were also lower in individuals with diabetes, the associations did not reach statistical significance.
Conclusions:
Among older adults with metabolic syndrome, higher bitter taste perception was associated with lower odds of being diagnosed with diabetes. Further investigations are warranted to confirm these observations and to determine whether bitter taste receptors may provide a possible therapeutic target for diabetes prevention and treatment.
Epidemiology studies suggested that low birthweight was associated with a higher risk of hypertension in later life. However, little is known about the causality of such associations. In our study, ...we evaluated the causal association of low birthweight with adulthood hypertension following a standard analytic protocol using the study-level data of 183,433 participants from 60 studies (CHARGE-BIG consortium), as well as that with blood pressure using publicly available summary-level genome-wide association data from EGG consortium of 153,781 participants, ICBP consortium and UK Biobank cohort together of 757,601 participants. We used seven SNPs as the instrumental variable in the study-level analysis and 47 SNPs in the summary-level analysis. In the study-level analyses, decreased birthweight was associated with a higher risk of hypertension in adults (the odds ratio per 1 standard deviation (SD) lower birthweight, 1.22; 95% CI 1.16 to 1.28), while no association was found between genetically instrumented birthweight and hypertension risk (instrumental odds ratio for causal effect per 1 SD lower birthweight, 0.97; 95% CI 0.68 to 1.41). Such results were consistent with that from the summary-level analyses, where the genetically determined low birthweight was not associated with blood pressure measurements either. One SD lower genetically determined birthweight was not associated with systolic blood pressure (β = − 0.76, 95% CI − 2.45 to 1.08 mmHg), 0.06 mmHg lower diastolic blood pressure (β = − 0.06, 95% CI − 0.93 to 0.87 mmHg), or pulse pressure (β = − 0.65, 95% CI − 1.38 to 0.69 mmHg, all p > 0.05). Our findings suggest that the inverse association of birthweight with hypertension risk from observational studies was not supported by large Mendelian randomization analyses.
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.
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.
Taste perception was cross-sectionally determined by challenging subjects (381 older individuals with MetS) with solutions (5 concentrations) of the basic tastes with the use of standard prototypical tastants (phenylthiocarbamide and 6-n-propylthiouracil, NaCl, sucrose, monopotassium glutamate, and citric acid, for bitter, salt, sweet, umami, and sour, respectively). Taste perception intensities were expressed on a scale. A total taste score was derived.
The total taste score was inversely associated with body weight, body mass index, and waist circumference (P < 0.05). Subjects having a total taste score higher than or equal to the median (11 points for concentration V) were less likely to be classified as obese than subjects below the median (OR: 0.36; 95% CI: 0.22, 0.59; P < 0.001). Associations were similar, albeit less strong, for some taste qualities. In the GWASs, the highest associations were for bitter taste (rs1726866-TAS2R38, with P = 7.74 × 10−18 for phenylthiocarbamide and P = 3.96 × 10−19 for 6-n-propylthiouracil). For other tastes, several single-nucleotide polymorphisms (SNPs) exceeded the P threshold of 1 × 10−5. However, the top-ranked SNPs independently explained a low percentage of taste variability, hence their use as single proxies for the association between taste perception and adiposity is limited.
We found a strong inverse association between greater taste perception and body weight, body mass index, and waist circumference in older subjects with MetS and identified some taste-related SNPs. It would be advantageous to identify additional genetic proxies for taste and to develop polygenic scores. Data used in this study were derived from the clinical trial PREDIMED PLUS at baseline, registered at http://www.isrctn.com as ISRCTN89898870.
Objective To examine whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal.Design Mendelian randomization study using the ...single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable.Setting CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium.Participants Data from 22 studies with 171 213 participants, and an additional 10 published prospective studies with 26 119 participants included in the observational analysis.Main outcome measures The instrumental variable estimation was conducted using the ratio of coefficients approach. Using meta-analysis, an additional eight published randomized clinical trials on the association of dairy consumption with systolic blood pressure were summarized.Results Compared with the CC genotype (CC is associated with complete lactase deficiency), the CT/TT genotype (TT is associated with lactose persistence, and CT is associated with certain lactase deficiency) of LCT-13910 (lactase persistence gene) rs4988235 was associated with higher dairy consumption (0.23 (about 55 g/day), 95% confidence interval 0.17 to 0.29) serving/day; P<0.001) and was not associated with systolic blood pressure (0.31, 95% confidence interval −0.05 to 0.68 mm Hg; P=0.09) or risk of hypertension (odds ratio 1.01, 95% confidence interval 0.97 to 1.05; P=0.27). Using LCT-13910 rs4988235 as the instrumental variable, genetically determined dairy consumption was not associated with systolic blood pressure (β=1.35, 95% confidence interval −0.28 to 2.97 mm Hg for each serving/day) or risk of hypertension (odds ratio 1.04, 0.88 to 1.24). Moreover, meta-analysis of the published clinical trials showed that higher dairy intake has no significant effect on change in systolic blood pressure for interventions over one month to 12 months (intervention compared with control groups: β=−0.21, 95% confidence interval −0.98 to 0.57 mm Hg). In observational analysis, each serving/day increase in dairy consumption was associated with −0.11 (95% confidence interval −0.20 to −0.02 mm Hg; P=0.02) lower systolic blood pressure but not risk of hypertension (odds ratio 0.98, 0.97 to 1.00; P=0.11).Conclusion The weak inverse association between dairy intake and systolic blood pressure in observational studies was not supported by a comprehensive instrumental variable analysis and systematic review of existing clinical trials.
Objective: The APOA2 gene has been associated with obesity and insulin resistance (IR) in animal and human studies with controversial results. We have reported an APOA2-saturated fat interaction ...determining body mass index (BMI) and obesity in American populations. This work aims to extend our findings to European and Asian populations. Methods: Cross-sectional study in 4602 subjects from two independent populations: a high-cardiovascular risk Mediterranean population (n=907 men and women; aged 67+/-6 years) and a multiethnic Asian population (n=2506 Chinese, n=605 Malays and n=494 Asian Indians; aged 39+/-12 years) participating in a Singapore National Health Survey. Anthropometric, clinical, biochemical, lifestyle and dietary variables were determined. Homeostasis model assessment of insulin resistance was used in Asians. We analyzed gene-diet interactions between the APOA2 -265T>C polymorphism and saturated fat intake (<or 22 g per day) on anthropometric measures and IR. Results: Frequency of CC (homozygous for the minor allele) subjects differed among populations (1-15%). We confirmed a recessive effect of the APOA2 polymorphism and replicated the APOA2-saturated fat interaction on body weight. In Mediterranean individuals, the CC genotype was associated with a 6.8% greater BMI in those consuming a high (P=0.018), but not a low (P=0.316) saturated fat diet. Likewise, the CC genotype was significantly associated with higher obesity prevalence in Chinese and Asian Indians only, with a high-saturated fat intake (P=0.036). We also found a significant APOA2-saturated fat interaction in determining IR in Chinese and Asian Indians (P=0.026). Conclusion: The influence of the APOA2 -265T>C polymorphism on body-weight-related measures was modulated by saturated fat in Mediterranean and Asian populations.
Abstract only
Introduction:
Emerging evidence suggests that differences in the ability to perceive individual tastes; sweet, salt, sour, bitter and umami, may influence food intake - amount and ...variety, thereby influencing diet quality, energy balance and cardiometabolic disorders.
Objective:
To explore the relationship between perception of each taste and intake of different categories of fruits and vegetables. We hypothesized that greater perception of each taste will be inversely associated with amount consumed.
Methods:
A cross-sectional analysis was performed on baseline data from participants (N=379) in the University of Valencia center of the PREDIMED-PLUS Clinical Trial; a multi-center weight-loss primary prevention trial of cardiovascular disease, among community-dwelling adults in Spain aged 55-75y diagnosed with metabolic syndrome. Taste perception was determined by challenging subjects with solutions of standard tastants representing 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). Taste perception intensities were evaluated on a 0-5 scale. Food intake was assessed using a validated food frequency questionnaire. Outcomes included fruit and vegetable intake (servings/week), total and sub-groups (citrus and non-citrus fruits; cruciferous and non-cruciferous vegetables). Multivariable linear regression models were used to assess relationships between perception of each tastant and number of servings/week consumed, for total and square root-transformed sub-groups.
Results:
In the fully-adjusted models, controlling for sex, age, diabetes, smoking status, daily physical activity and weekly energy intake, there were inverse associations between sweet perception and intake of citrus fruit (β=-0.5; p<0.01) and total vegetables (β=-1.1; 95% CI -2.0, -0.2), particularly non-cruciferous vegetables (β=-1.0; p=0.02); and positive associations between salt perception and intake of total fruit (β=0.9; 95% CI 0.02, 1.7), particularly non-citrus fruit (β=0.6; p=0.03), sour perception and intake of cruciferous vegetables (β=0.1; p=0.04) and umami perception and intake of non-cruciferous vegetables (β=0.7; p=0.04). No significant associations were observed between bitter taste perception and fruit or vegetable intake.
Conclusion:
This marks the first exploration of taste perception as a determinant of fruit and vegetable intake among community-dwelling adults. Perception for each tastant differentially affected the amount and type of fruits and vegetables consumed, with sweet, salt, sour and umami perception emerging as significant predictors. These findings support a role of taste perception in guiding the amount and type of foods consumed, albeit in a more complex manner than originally hypothesized.
Impaired sense of smell is a predictor of morbidity and mortality, including cardiovascular diseases. Likewise, several studies have reported sex-specific associations between olfactory function and ...cardiometabolic measures including plasma lipids and blood pressure. Thus, in a representative sample of US adults from the National Health and Nutrition Examination Survey (NHANES) study, olfactory dysfunction was associated with significantly higher total cholesterol (TC) and LDL-C among older men, but significantly lower TC among older women. However, considering that more studies in diverse population are needed, our aim was to analyze the association between the olfactory dysfunction and plasma lipids and blood pressure in older European subjects at high cardiovascular risk.
We measured olfactory function in 300 high-cardiovascular risk participants (older subjects with metabolic syndrome, aged 65+/-5y, 54.7% women) using the validated Sniffin' Sticks Extended test. We calculated the “TDI-score”, whose value is the sum of the results obtained for individual tests on threshold detection, discrimination, and identification of 16 odors. The higher the score, the greater olfactory function. Hyposmia was defined as TDI-score<30. Multivariate regression models adjusted for confounders: age, sex, body mass index, diabetes, medications, and smoking were fitted to test the association between hyposmia and the cardiometabolic parameters.
Hyposmia prevalence was 70%, being higher in males (P=0.040). In the whole population, hyposmia was associated with lower diastolic blood pressure (P=0.044). However, for lipids, we found associations varying by sex. Thus, fasting triglycerides were higher in males with hyposmia, but lower among females with hyposmia (P-for-sex-hyposmia-interaction=0.037).
PDF
