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 "total taste score") and their modulation by sex and genetics in a relatively healthy population (men and women) aged 18⁻80 years (
= 1020 Caucasian European participants). Taste perception was determined by challenging subjects with solutions of the five basic tastes using standard prototypical tastants (6-n-propylthiouracil (PROP), NaCl, sucrose, monopotassium glutamate and citric acid) at 5 increasing concentrations (I to V). We also measured taste preferences and determined the polymorphisms of the genes taste 2 receptor member 38 (TAS2R38), taste 1 receptor member 2 (TAS2R38) and sodium channel epithelial 1 beta subunit (SCNN1B), as TAS2R38-rs713598, TAS1R2-rs35874116 and SCNN1B-rs239345 respectively. We found a statistically significant decrease in taste perception ("total taste score") with increasing age for all the concentrations analysed. This association was stronger for the higher concentrations (
= 0.028;
= 0.012;
= 0.005;
= 4.20 × 10
and
= 1.48 × 10
, for I to V in the multivariable-adjusted models). When we analysed taste qualities (using concentration V), the intensity rating of all the 5 tastes was diminished with age (
0.05 for all). This inverse association differed depending on the test quality, being higher for bitter (PROP) and sour. Women perceived taste significantly more intense than men (
= 1.4 × 10
for total taste score). However, there were differences depending on the taste, umami being the lowest (
= 0.069). There was a complex association between the ability to perceive a taste and the preference for the same. Significant associations were, nevertheless, found between a higher perception of sour taste and a higher preference for it in women. In contrast, the higher perception of sweet was significantly associated with a higher preference for bitter in both, men and women. The TAS2R38-rs713598 was strongly associated with bitter (PROP) taste (
= 1.38 × 10
), having a significant interaction with sex (
= 0.030). The TAS1R2-rs35874116 was not significantly associated with sweet, whereas the SCNN1B-rs239345 was associated (
= 0.040) with salty taste. In conclusion, the inverse association between age and perceived taste intensity as well as the additional influence of sex and some genetic polymorphisms give rise to large inter-individual differences in taste perception and taste preferences that should be taken into account in future studies and for applications in precision nutrition for healthy aging.
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 association of the GRS with plasma concentrations of antioxidant vitamins (C and E). We carried out a case-control study including 391 POAG cases and 383 healthy controls, and analyzed four genetic polymorphisms (rs4656461-
, rs4236601-
/
, rs2157719-
and rs3088440-
). An unweighted GRS including the four non-linked polymorphisms was constructed. A strong association between the GRS and POAG risk was found. When three categories of the GRS were considered, subjects in the top category of the GRS were 2.92 (95% confidence interval (CI): 1.79-4.77) times more likely to have POAG compared with participants in the bottom category (
< 0.001). Moreover, the GRS was inversely correlated with plasma vitamin C (
= 0.002) and vitamin E (
= 0.001) concentrations, even after additional adjustment for POAG status. In conclusion, we have found a strong association between the GRS and POAG risk in this Mediterranean population. While the additional correlation found between GRS and low levels of vitamins C and E does not indicated a causal relationship, it does suggest the need for new and deeper research into the effects of oxidative stress as a potential mechanism for those associations.
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.
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.
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 but remained statistically significant (TT vs. CC: odds ratios = 2.07, 95% confidence interval = 1.20–3.57).
Conclusion
This polymorphism seems to be associated with high risk for primary open‐angle glaucoma in a Mediterranean population.
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.
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 biomarkers associated with orange consumption (
) in plasma samples taken during an acute intervention study (consisting of a randomized, controlled crossover trial in healthy individuals). A total of six markers of acute orange consumption, including betonicines and conjugated flavonoids, were identified with the experimental data and previous literature, demonstrating the advantages of ion mobility in the identification of dietary biomarkers and the benefits that an additional structural descriptor, as the collision cross section value (CCS), can provide in this area.
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.
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 gene variation and T2D or CVD incidence. Moreover, although in a previous work we detected a gene-diet interaction between the CLOCK-rs4580704 (C > G) single nucleotide polymorphism (SNP) and monounsaturated (MUFA) intake on insulin resistance, no interventional study has analyzed gene-diet interactions on T2D or CVD outcomes.
We analyzed the association between the CLOCK-rs4580704 SNP and incidence of T2D and CVD longitudinally in 7098 PREDIMED trial (ISRCTN35739639) participants after a median 4.8-year follow-up. We also examined modulation by Mediterranean diet (MedDiet) intervention (high in MUFA) on these associations.
We observed a significant association between the CLOCK-rs4580704 SNP and T2D incidence in n = 3671 non-T2D PREDIMED participants, with variant allele (G) carriers showing decreased incidence (dominant model) compared with CC homozygotes (HR: 0.69; 95 % CI 0.54-0.87; P = 0.002). This protection was more significant in the MedDiet intervention group (HR: 0.58; 95 % CI 0.43-0.78; P < 0.001) than in the control group (HR: 0.95; 95 % CI 0.63-1.44; P = 0.818). Moreover, we detected a statistically significant interaction (P = 0.018) between CLOCK-rs4580704 SNP and T2D status on stroke. Thus, only in T2D subjects was CLOCK-rs4580704 SNP associated with stroke risk, G-carriers having decreased risk (HR: 0.61; 95 % CI 0.40-0.94; P = 0.024 versus CC) in the multivariable-adjusted model.
In agreement with our previous results showing a protective effect of the G-allele against hyperglycemia, we extended our findings by reporting a novel association with lower T2D incidence and also suggesting a dietary modulation. Moreover, we report for the first time an association between a CLOCK polymorphism and stroke in T2D subjects, suggesting that core clock genes may significantly contribute to increased CVD risk in T2D.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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 baseline and after a median follow-up of 4.8 years. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) for cardiovascular events.
The TCF7L2-rs7903146 polymorphism was associated with type 2 diabetes (odds ratio 1.87 95% CI 1.62-2.17 for TT compared with CC). MedDiet interacted significantly with rs7903146 on fasting glucose at baseline (P interaction = 0.004). When adherence to the MedDiet was low, TT had higher fasting glucose concentrations (132.3 ± 3.5 mg/dL) than CC+CT (127.3 ± 3.2 mg/dL) individuals (P = 0.001). Nevertheless, when adherence was high, this increase was not observed (P = 0.605). This modulation was also detected for total cholesterol, LDL cholesterol, and triglycerides (P interaction < 0.05 for all). Likewise, in the randomized trial, TT subjects had a higher stroke incidence in the control group (adjusted HR 2.91 95% CI 1.36-6.19; P = 0.006 compared with CC), whereas dietary intervention with MedDiet reduced stroke incidence in TT homozygotes (adjusted HR 0.96 95% CI 0.49-1.87; P = 0.892 for TT compared with CC).
Our novel results suggest that MedDiet may not only reduce increased fasting glucose and lipids in TT individuals, but also stroke incidence.
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