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 (
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 (GWAS) have been carried out in other populations and none of them have investigated sex and Mediterranean dietary pattern interactions at the genome-wide level. Our aims were to undertake a GWAS to discover the genes most associated with serum PUFA concentrations (omega-3, omega-6, and some fatty acids) in a scarcely studied Mediterranean population with metabolic syndrome, and to explore sex and adherence to Mediterranean diet (MedDiet) interactions at the genome-wide level. Serum PUFA were determined by NMR spectroscopy. We found strong robust associations between various SNPs in the
cluster and omega-3 concentrations (top-ranked in the adjusted model:
-rs174547,
= 3.34 × 10
;
-rs174550,
= 5.35 × 10
;
-rs1535,
= 5.85 × 10
;
-rs174546,
= 6.72 × 10
;
-rs174546,
= 9.75 × 10
;
- rs174576,
= 1.17 × 10
;
-rs174577,
= 1.12 × 10
, among others). We also detected a genome-wide significant association with other genes in chromosome 11:
(myelin regulatory factor)-rs174535,
= 1.49 × 10
;
(transmembrane protein 258)-rs102275,
= 2.43 × 10
;
(flap structure-specific endonuclease 1)-rs174538,
= 1.96 × 10
). Similar genome-wide statistically significant results were found for docosahexaenoic fatty acid (DHA). However, no such associations were detected for omega-6 PUFAs or linoleic acid (LA). For total PUFA, we observed a consistent gene*sex interaction with the
(deoxynucleotidyl transferase terminal interacting protein 2)-rs3747965
= 1.36 × 10
. For adherence to MedDiet, we obtained a relevant interaction with the
(malic enzyme 1) gene (a gene strongly regulated by fat) in determining serum omega-3. The top-ranked SNP for this interaction was
-rs3798890 (
= 2.15 × 10
). In the regional-wide association study, specifically focused on the
and
(fatty acid elongase) 2/
5 regions, we detected several statistically significant associations at
< 0.05. In conclusion, our results confirm a robust role of the
cluster on serum PUFA in this population, but the associations vary depending on the PUFA. Moreover, the detection of some sex and diet interactions underlines the need for these associations/interactions to be studied in all specific populations so as to better understand the complex metabolism of PUFA.
Aging is a risk factor for several pathologies, restricting one's health span, and promoting chronic diseases (e.g., cardiovascular and neurodegenerative diseases), as well as cancer. Telomeres are ...regions of repetitive DNA located at chromosomal ends. Telomere length has been inversely associated with chronological age and has been considered, for a long time, a good biomarker of aging. Several lifestyle factors have been linked with telomere shortening or maintenance. However, the consistency of results is hampered by some methodological issues, including study design, sample size, measurement approaches, and population characteristics, among others. Therefore, we aimed to systematically review the current literature on the effects of three relevant lifestyle factors on telomere length in human adults: physical activity, smoking, and sleep. We conducted a qualitative systematic review of observational and intervention studies using the Preferred Reporting Item for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The systematic literature search covered articles published in MEDLINE and EMBASE databases (from 2010 to 2020). A total of 1400 studies were identified; 83 were included after quality control. Although fewer sedentary activities, optimal sleep habits, and non- or ex-smoker status have been associated with less telomere shortening, several methodological issues were detected, including the need for more targeted interventions and standardized protocols to better understand how physical activity and sleep can impact telomere length and aging. We discuss the main findings and current limitations to gain more insights into the influence of these lifestyle factors on the healthy aging process.
DNA-methylation has been associated with biological age and several epigenetic clocks have been reported (Hovarth) MicroRNA (miRNA) are short single-stranded RNA molecules implicated in the ...regulation of gene expression. As well as protein-coding genes, miRNA-coding genes may be targets for DNA methylation. However, the role of this methylation on aging and cardiovascular risk is still poorly studied. Our aim is to analyze the DNA methylation in miRNA-coding genes in a high-cardiovascular risk Mediterranean population, and its association with age considering sex-specific differences.
A DNA-methylation analysis of miRNA genes was analyzed using the EPIC850K array, in high-cardiovascular risk 414 subjects aged 55-75y. We obtained Beta and M-values for CpGs located in the miRNA genes and their association with age in multivariate models adjusted for confounders (sex, leukocytes, batch-effect, diabetes, BMI). Sex-specific analyses were conducted.
In the whole population, significant associations between miRNA-gene methylation and chronological age were obtained. Outstanding the MIR34B (cg26561785; p=3,9 × 10-8; hypermethylation associated with higher age; r=0.28). Previous studies have linked miR-34a to vascular aging and arteriosclerosis. The following most significant associations (p=4,7 × 10-7-1,5 × 10-6) were obtained with CpG in MIR663(r=0.26), MIR9-3(r=0.26), MIR495(r=-0.26) and MIR203A(r=0.25), as main components of the methylation signature in the whole population. Sex-specific analysis detected sex-specific differences. The top-ranked CpGs in men were MIR34B (cg26561785;p=9.2 × 10-6) and MIR9-3 (cg12530503;p=1.8 × 10-05); whereas in women were MIR376B (cg05348084;p=4.3 × 10-7) and MIR203A (cg24454784;p=3.9 × 10-06).
Altered methylation in MIR genes is associated with chronological age, and this association may be different between men and women with high-cardiovascular risk.
Background Insufficient sleep is associated with increased cardiovascular disease risk, but causality is unclear. We investigated the impact of prolonged mild sleep restriction (SR) on lipid and ...inflammatory profiles. Methods and Results Seventy-eight participants (56 women 12 postmenopausal; age, 34.3±12.5 years; body mass index, 25.8±3.5 kg/m
) with habitual sleep duration 7 to 9 h/night (adequate sleep AS) underwent two 6-week conditions in a randomized crossover design: AS versus SR (AS-1.5 h/night). Total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, and inflammatory markers (CRP C-reactive protein, interleukin 6, and tumor necrosis factor-α) were assessed. Linear models tested effects of SR on outcomes in the full sample and by sex+menopausal status (premenopausal versus postmenopausal women+men). In the full sample, SR increased high-density lipoprotein cholesterol compared with AS (β=1.2±0.5 mg/dL;
=0.03). Sex+menopausal status influenced the effects of SR on change in total cholesterol (
-interaction=0.04), LDL-C (
-interaction=0.03), and interleukin 6 (
-interaction=0.07). Total cholesterol and LDL-C decreased in SR versus AS in premenopausal women (total cholesterol: β=-4.2±1.9 mg/dL;
=0.03; LDL-C: β=-6.3±2.0 mg/dL;
=0.002). Given paradoxical effects of SR on cholesterol concentrations, we explored associations between changes in inflammation and end point lipids under each condition. Increases in interleukin 6 and tumor necrosis factor-α during SR tended to relate to lower LDL-C in premenopausal women (interleukin 6: β=-5.3±2.6 mg/dL;
=0.051; tumor necrosis factor-α: β=-32.8±14.2 mg/dL;
=0.027). Conclusions Among healthy adults, prolonged insufficient sleep does not increase atherogenic lipids. However, increased inflammation in SR tends to predict lower LDL-C in premenopausal women, resembling the "lipid paradox" in which low cholesterol associates with increased cardiovascular disease risk in proinflammatory conditions. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02835261, NCT02960776.
Poor sleep is a determinant of obesity, with overconsumption of energy contributing to this relationship. Eating behavior characteristics are predictive of energy intake and weight change and may ...underlie observed associations of sleep with weight status and obesity risk factors. However, relationships between sleep and dimensions of eating behavior, as well as possible individual differences in these relations, are not well characterized. Therefore, the aim of this study was to evaluate whether sleep behaviors, including duration, timing, quality, and regularity relate to dietary restraint, disinhibition, and tendency towards hunger and to explore whether these associations differ by sex. This cross-sectional study included 179 adults aged 20-73 years (68.7% women, 64.8% with BMI ≥ 25 kg/m
). Sleep was evaluated by accelerometry over 2 weeks. Eating behavior dimensions were measured with the Three-Factor Eating Questionnaire. Prolonged wake after sleep onset (WASO) (0.029 ± 0.011,
= 0.007), greater sleep fragmentation index (0.074 ± 0.036,
= 0.041), and lower sleep efficiency (-0.133 ± 0.051,
= 0.010) were associated with higher dietary restraint. However, higher restraint attenuated associations of higher WASO and sleep fragmentation with higher BMI (
-interactions < 0.10). In terms of individual differences, sex influenced associations of sleep quality measures with tendency towards hunger (
-interactions < 0.10). Stratified analyses showed that, in men only, higher sleep fragmentation index, longer sleep onset latency, and lower sleep efficiency were associated with greater tendency towards hunger (β = 0.115 ± 0.037,
= 0.003, β = 0.169 ± 0.072,
= 0.023, β = -0.150 ± 0.055,
= 0.009, respectively). Results of this analysis suggest that the association of poor sleep on food intake could be exacerbated in those with eating behavior traits that predispose to overeating, and this sleep-eating behavior relation may be sex-dependent. Strategies to counter overconsumption in the context of poor quality sleep should be evaluated in light of eating behavior traits.
Adiponectin is gaining renewed interest since, in addition to its possible protective role against insulin resistance and arteriosclerosis, recent studies suggest other additional favorable effects. ...However, the influence of gene-diet interactions on plasma adiponectin levels is still little understood. We analyzed the association between plasma adiponectin levels and various metabolic traits in a high-cardiovascular risk Mediterranean population, as well as the genetic effect of four candidate single-nucleotide polymorphisms (SNPs) in the adiponectin gene (
) and their interactions with the Mediterranean dietary pattern. Additionally, we explored, at the genome-wide level, the SNPs most associated with plasma adiponectin levels, as well as gene-diet interactions with the Mediterranean diet. In the 954 participants studied (aged 55-80 years), plasma adiponectin levels were strongly associated with plasma HDL-C concentrations (
= 6.6 × 10
) and inversely related to triglycerides (
= 4.7 × 10
), fasting glucose (
= 3.5 × 10
) and type 2 diabetes (
= 1.4 × 10
). Of the four pre-selected
candidate SNPs, the one most associated with plasma adiponectin was the -11391G > A (rs17300539) promoter SNP (
= 7.2 × 10
, in the multivariable adjusted model). No significant interactions with the Mediterranean diet pattern were observed for these SNPs. Additionally, in the exploratory genome-wide association study (GWAS), we found new SNPs associated with adiponectin concentrations at the suggestive genome-wide level (
< 1 × 10
) for the whole population, including the lead SNP rs9738548 (intergenic) and rs11647294 in the
(Vesicle Amine Transport 1 Like) gene. We also found other promising SNPs on exploring different strata such as men, women, diabetics and non-diabetics (
= 3.5 × 10
for rs2850066). Similarly, we explored gene-Mediterranean diet interactions at the GWAS level and identified several SNPs with gene-diet interactions at
< 1 × 10
. A remarkable gene-diet interaction was revealed for the rs2917570 SNP in the
(Opioid Binding Protein/Cell Adhesion Molecule Like) gene, previously reported to be associated with adiponectin levels in some populations. Our results suggest that, in this high-cardiovascular risk Mediterranean population, and even though adiponectin is favorably associated with metabolic traits and lower type 2 diabetes, the gene variants more associated with adiponectin may be population-specific, and some suggestive gene-Mediterranean diet interactions were detected.
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.
Circadian rhythms regulate the sleep-wake and feeding-fasting cycles. Sleep and feeding constitute a complex cycle that is determined by several factors. Despite the importance of sleep duration and ...mealtimes for many obesity phenotypes, most studies on dietary patterns have not investigated the contribution of these variables to the phenotypes analyzed. Likewise, they have not investigated the factors related to sleep or mealtimes. Thus, our aims were to investigate the link between taste perception and eating/sleep patterns and to analyze the effect of the interactions between sleep/meal patterns and genetic factors on obesity phenotypes. We conducted a cross-sectional analysis on 412 adults from the Mediterranean population. We measured taste perception (bitter, sweet, salty, sour, and umami) and assessed sleep duration and waketime. The midpoint of sleep and social jetlag was computed. From the self-reported timing of meals, we estimated the eating window, eating midpoint, and eating jetlag. Adherence to the Mediterranean diet was measured with a validated score. Selected polymorphisms in the TAS2R38, CLOCK, and FTO genes were determined, and their associations and interactions with relevant phenotypes were analyzed. We found various associations between temporal eating, sleep patterns, and taste perception. A higher bitter taste perception was associated with an earlier eating midpoint (
= 0.001), breakfast time (
= 0.043), dinner time (
= 0.009), waketime (
< 0.001), and midpoint of sleep (
= 0.009). Similar results were observed for the bitter taste polymorphism TAS2R38-rs713598, a genetic instrumental variable for bitter perception, increasing the causality of the associations. Moreover, significant gene-sleep interactions were detected between the midpoint of sleep and the TAS2R38-rs713598 (
= 0.032), FTO-rs9939609 (
= 0.037), and CLOCK-rs4580704 (
= 0.004) polymorphisms which played a role in determining obesity phenotypes. In conclusion, our study provided more information on the sleep and mealtime patterns of the general Spanish Mediterranean population than on their main relationships. Moreover, we were able to show significant associations between taste perception, specifically bitter taste; sleep time; and mealtimes as well as an interaction between sleep time and several genetic variants linked to obesity phenotypes. However, additional research is needed to better characterize the causality and mechanisms behind these associations.
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 through inductively coupled plasma mass spectrometry (ICP-MS)) methods, and cardiovascular risk factors in individuals from a general Mediterranean population (aged 18-80 years). The influence of demographic and lifestyle variables, including adherence to the Mediterranean diet, on plasma Mg concentrations was analyzed. The mean Mg level of the population studied was 0.77 ± 0.08 mmol/L, the prevalence of hypomagnesemia (<0.70 mmol/L) being 18.6%. We did not find any statistically significant differences between plasma Mg concentrations and sex, age, tobacco smoking and total adherence to the Mediterranean diet (
> 0.05). We found a statistically significant association between plasma Mg concentrations and the prevalence of type-2 diabetes (0.77 ± 0.08 mmol/L in non-diabetics versus 0.73 ± 0.13 mmol/L in diabetics;
= 0.009). Despite the low prevalence of type-2 diabetes in this population (11.24% in subjects with hypomagnesemia versus 3.91%, in normomagnesemia;
= 0.005), hypomagnesemia was associated with greater odds of being diabetic in comparison with normomagnesemia (OR = 3.36;
= 0.016, even after adjustment for sex, age, obesity, and medications). On the other hand, no statistically significant association of plasma Mg concentrations with obesity, hypertension, fasting triglycerides, HDL-cholesterol or uric acid was found. However, in contrast to what was initially expected, a statistically significant association was found between plasma Mg concentrations (basically in the highest quartile) and greater total cholesterol (
< 0.05) and LDL-cholesterol concentrations (
< 0.05). In conclusion, our results contribute to increasing the evidence gathered by numerous studies on the inverse association between hypomagnesemia and type-2 diabetes, as well as to the observation, previously reported in some studies, of a direct association with hypercholesterolemia. This paradoxical link should be deeply investigated in further studies.
Recently, microRNAs (miRNA) have been proposed as regulators in the different processes involved in alcohol intake, and differences have been found in the miRNA expression profile in alcoholics. ...However, no study has focused on analyzing polymorphisms in genes encoding miRNAs and daily alcohol consumption at the population level. Our aim was to investigate the association between a functional polymorphism in the pre-miR-27a (rs895819 A>G) gene and alcohol consumption in an elderly population. We undertook a cross-sectional study of PREvención con DIeta MEDiterránea (PREDIMED)-Valencia participants (n = 1007, including men and women aged 67 ± 7 years) and measured their alcohol consumption (total and alcoholic beverages) through a validated questionnaire. We found a strong association between the pre-miR-27a polymorphism and total alcohol intake, this being higher in GG subjects (5.2 ± 0.4 in AA, 5.9 ± 0.5 in AG and 9.1 ± 1.8 g/day in GG; padjusted = 0.019). We also found a statistically-significant association of the pre-miR-27a polymorphism with the risk of having a high alcohol intake (>2 drinks/day in men and >1 in women): 5.9% in AA versus 17.5% in GG; padjusted < 0.001. In the sensitivity analysis, this association was homogeneous for sex, obesity and Mediterranean diet adherence. In conclusion, we report for the first time a significant association between a miRNA polymorphism (rs895819) and daily alcohol consumption.
PDF
