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.
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).
Case-control study in 7,052 high cardiovascular risk subjects (3,430 type 2 diabetes cases and 3,622 non-diabetic subjects) with no differences in BMI. Diet was assessed by validated questionnaires. FTO-rs9939609 and MC4R-rs17782313 were determined. An aggregate genetic score was calculated to test additive effects. Gene-diet interactions were analyzed.
Neither of the polymorphisms was associated with type 2 diabetes in the whole population. However, we found consistent gene-diet interactions with adherence to the MedDiet both for the FTO-rs9939609 (P-interaction=0.039), the MC4R-rs17782313 (P-interaction=0.009) and for their aggregate score (P-interaction=0.006). When adherence to the MedDiet was low, carriers of the variant alleles had higher type 2 diabetes risk (OR=1.21, 95%CI: 1.03-1.40; P=0.019 for FTO-rs9939609 and OR=1.17, 95%CI:1.01-1.36; P=0.035 for MC4R-rs17782313) than wild-type subjects. However, when adherence to the MedDiet was high, these associations disappeared (OR=0.97, 95%CI: 0.85-1.16; P=0.673 for FTO-rs9939609 and OR=0.89, 95%CI:0.78-1.02; P=0.097 for MC4R-rs17782313). These gene-diet interactions remained significant even after adjustment for BMI. As MedDiet is rich in folate, we also specifically examined folate intake and detected statistically significant interaction effects on fasting plasma glucose concentrations in non-diabetic subjects. However these findings should be interpreted with caution because folate intake may simply reflect a healthy dietary pattern.
These novel results suggest that the association of the FTO-rs9939609 and the MC4R-rs17782313 polymorphisms with type 2 diabetes depends on diet and that a high adherence to the MedDiet counteracts the genetic predisposition.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Taste perception is a primary driver of food choices; however, little is known about how perception of all five tastes (sweet, salt, sour, bitter, umami) collectively inform dietary patterns. Our aim ...was to examine the associations between a multivariable measure of taste perception-taste perception profiles-and empirically derived dietary patterns. The cohort included 367 community-dwelling adults (55-75 years; 55% female; BMI = 32.2 ± 3.6 kg/m
) with metabolic syndrome from PREDIMED-Plus, Valencia. Six taste perception profiles were previously derived via data-driven clustering (Low All, High Bitter, High Umami, Low Bitter and Umami, High All But Bitter, High All But Umami); three dietary patterns were derived via principal component analysis (% variance explained = 20.2). Cross-sectional associations between profiles and tertials of dietary pattern adherence were examined by multinomial logistic regression. Overall, there were several significant differences in dietary pattern adherence between profiles: the vegetables, fruits, and whole grains pattern was significantly more common for the High All But Umami profile (OR range for high vs. low adherence relative to other profiles (1.45-1.99; 95% CI minimum lower, maximum upper bounds: 1.05, 2.74), the non-extra virgin olive oils, sweets, and refined grains pattern tended to be less common for Low All or High Bitter profiles (OR range: 0.54-0.82), while the alcohol, salty foods, and animal fats pattern tended to be less common for Low Bitter and Umami and more common for High All But Bitter profiles (OR range: 0.55-0.75 and 1.11-1.81, respectively). In conclusion, among older adults with metabolic syndrome, taste perception profiles were differentially associated with dietary patterns, suggesting the benefit of integrating taste perception into personalized nutrition guidance.
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.
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. 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. 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 associations (aggregate genetic score) as well as statistical and biological gene-lifestyle interactions were analyzed. FTO rs9939609 was associated with higher body mass index (BMI), waist circumference (WC) and obesity (P<0.05 for all). A similar, but not significant trend was found for MC4R rs17782313. Their additive effects (aggregate score) were significant and we observed a 7% per-allele increase of being obese (OR = 1.07; 95%CI 1.01–1.13). We found relevant statistical interactions (P<0.05) with PA. So, in active individuals, the associations with higher BMI, WC or obesity were not detected. A biological (non-statistical) interaction between AdMedDiet and rs9939609 and the aggregate score was found. Greater AdMedDiet in individuals carrying 4 or 3-risk alleles counterbalanced their genetic predisposition, exhibiting similar BMI (P = 0.502) than individuals with no risk alleles and lower AdMedDiet. They also had lower BMI (P = 0.021) than their counterparts with low AdMedDiet. We did not find any consistent association with energy or macronutrients, but found a novel association between these polymorphisms and lower alcohol consumption in variant-allele carriers (B+/−SE: −0.57+/−0.16 g/d per-score-allele; P = 0.001). Statistical and biological interactions with PA and diet modulate the effects of FTO and MC4R polymorphisms on obesity. The novel association with alcohol consumption seems independent of their effects on BMI.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and Objectives: Circadian rhythms have an important implication in numerous physiological and metabolic processes, including the sleep/wake cycle. Inter-individual differences in factors ...associated with circadian system may be due to gene differences in gene expression. Although several studies have analyzed the association between DNA polymorphisms and circadian variables, the influence on gene expression has been poorly analyzed. Our goal was to analyze the association of genetic variations in the clock genes and the gene expression level. Materials and Methods: We carried out a cross-sectional study of 102 adults (50.9% women). RNA and DNA were isolated from blood and single-nucleotide polymorphisms (SNPs), and the main circadian clock genes were determined. Gene expression of CLOCK, PER1, and VRK2 genes was measured by Reverse-transcription polymerase chain reaction (RT-PCR). The association between the DNA-SNPs and gene expression was analyzed at the gene level. In addition, a polygenic risk score (PRS), including all the significant SNPs related to gene expression, was created for each gene. Multivariable model analysis was performed. Results: Sex-specific differences were detected in PER1 expression, with these being higher in women (p = 0.034). No significant differences were detected in clock genes expression and lifestyle variables. We observed a significant association between the ARNTL-rs7924734, ARNTL-rs10832027, VRK2- rs2678902 SNPs, and CLOCK gene expression; the PER3-rs228642 and PER3-rs10127838 were related to PER1 expression, and the ARNTL-rs10832027, ARNTL-rs11022778, and MNTR1B-rs10830963 were associated with VRK2 gene expression (p < 0.05). The specific PRS created was significantly associated with each of the gene expressions analyzed (p < 0.001). Finally, sleep duration was associated with PER3-rs238666 (p = 0.008) and CLOCK-rs4580704 (p = 0.023). Conclusion: We detected significant associations between DNA-SNPs in the clock genes and their gene expression level in leukocytes and observed some differences in gene expression per sex. Moreover, we reported for the first time an association between clock gene polymorphisms and CLOCK, PER1, and VRK2 gene expression. These findings need further investigation.
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.
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>G variant that has been associated with fasting glucose concentrations, gestational diabetes, and type-2 diabetes. Therefore, our main aim was to investigate whether the association between the MTNR1B-rs10830963 polymorphism and fasting glucose is age dependent. Our secondary aims were to analyze the polymorphism association with type-2 diabetes and explore the gene-pregnancies interactions on the later type-2 diabetes risk. Three Mediterranean cohorts (
= 2823) were analyzed. First, a cross-sectional study in the discovery cohort consisting of 1378 participants (aged 18 to 80 years; mean age 41 years) from the general population was carried out. To validate and extend the results, two replication cohorts consisting of elderly individuals were studied. In the discovery cohort, we observed a strong gene-age interaction (
= 0.001), determining fasting glucose in such a way that the increasing effect of the risk G-allele was much greater in young (
= 5.9 × 10
) than in elderly participants (
= 0.805). Consistently, the association of the MTNR1B-rs10830963 polymorphism with fasting glucose concentrations in the two replication cohorts (mean age over 65 years) did not reach statistical significance (
> 0.05 for both). However, in the elderly cohorts, significant associations between the polymorphism and type-2 diabetes at baseline were found. Moreover, in one of the cohorts, we obtained a statistically significant interaction between the MTNR1B polymorphism and the number of pregnancies, retrospectively assessed, on the type-2 diabetes risk. In conclusion, the association of the MTNR1B-rs10830963 polymorphism with fasting glucose is age-dependent, having a greater effect in younger people. However, in elderly subjects, associations of the polymorphism with type-2 diabetes were observed and our exploratory analysis suggested a modulatory effect of the number of past pregnancies on the future type-2 diabetes genetic risk.
Nutrigenetic studies analyzing gene-diet interactions of the TCF7L2-rs7903146 C > T polymorphism on type-2 diabetes (T2D) have shown controversial results. A reason contributing to this may be the ...additional modulation by obesity. Moreover, TCF7L2-rs7903146 is one of the most influential variants in T2D-genetic risk scores (GRS). Therefore, to increase the predictive value (PV) of GRS it is necessary to first see whether the included polymorphisms have heterogeneous effects. We comprehensively investigated gene-obesity interactions between the TCF7L2-rs7903146 C > T polymorphism on T2D (prevalence and incidence) and analyzed other T2D-polymorphisms in a sub-sample. We studied 7018 PREDIMED participants at baseline and longitudinally (8.7 years maximum follow-up). Obesity significantly interacted with the TCF7L2-rs7903146 on T2D prevalence, associations being greater in non-obese subjects. Accordingly, we prospectively observed in non-T2D subjects (
= 3607) that its association with T2D incidence was stronger in non-obese (HR: 1.81; 95% CI: 1.13-2.92,
= 0.013 for TT versus CC) than in obese subjects (HR: 1.01; 95% CI: 0.61-1.66;
= 0.979;
-interaction = 0.048). Accordingly, TCF7L2-PV was higher in non-obese subjects. Additionally, we created obesity-specific GRS with ten T2D-polymorphisms and demonstrated for the first time their higher strata-specific PV. In conclusion, we provide strong evidence supporting the need for considering obesity when analyzing the TCF7L2 effects and propose the use of obesity-specific GRS for T2D.
Trace elements are micronutrients that are required in very small quantities through diet but are crucial for the prevention of acute and chronic diseases. Despite the fact that initial studies ...demonstrated inverse associations between some of the most important essential trace elements (Zn, Cu, Se, and Mn) and cardiovascular disease, several recent studies have reported a direct association with cardiovascular risk factors due to the fact that these elements can act as both antioxidants and pro-oxidants, depending on several factors. This study aims to investigate the association between plasma and urine concentrations of trace elements and cardiovascular risk factors in a general population from the Mediterranean region, including 484 men and women aged 18−80 years and considering trace elements individually and as joint exposure. Zn, Cu, Se, and Mn were determined in plasma and urine using an inductively coupled plasma mass spectrometer (ICP-MS). Single and combined analysis of trace elements with plasma lipid, blood pressure, diabetes, and anthropometric variables was undertaken. Principal component analysis, quantile-based g-computation, and calculation of trace element risk scores (TERS) were used for the combined analyses. Models were adjusted for covariates. In single trace element models, we found statistically significant associations between plasma Se and increased total cholesterol and systolic blood pressure; plasma Cu and increased triglycerides and body mass index; and urine Zn and increased glucose. Moreover, in the joint exposure analysis using quantile g-computation and TERS, the combined plasma levels of Zn, Cu, Se (directly), and Mn (inversely) were strongly associated with hypercholesterolemia (OR: 2.03; 95%CI: 1.37−2.99; p < 0.001 per quartile increase in the g-computation approach). The analysis of urine mixtures revealed a significant relationship with both fasting glucose and diabetes (OR: 1.91; 95%CI: 1.01−3.04; p = 0.046). In conclusion, in this Mediterranean population, the combined effect of higher plasma trace element levels (primarily Se, Cu, and Zn) was directly associated with elevated plasma lipids, whereas the mixture effect in urine was primarily associated with plasma glucose. Both parameters are relevant cardiovascular risk factors, and increased trace element exposures should be considered with caution.
PDF
