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Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of liver-related morbidity and mortality. Although the invasive liver biopsy remains the golden standard for MASLD diagnosis, Magnetic Resonance Imaging-derived Proton Density Fat Fraction (MRI-PDFF) is an accurate, non-invasive method for the assessment of treatment response. This study aimed at developing a Polygenic Risk Score (PRS) to improve MRI-PDFF prediction using UK Biobank data to assess an individual's genetic liability to MASLD., Methods: We iteratively sequestered 10% of MRI-PDFF samples as a validation set and split the rest of each dataset into base and target partitions, containing GWAS summary statistics and raw genotype data, respectively. PRSice2 was deployed to derive PRS candidates. Based on the frequency of SNP appearances along the PRS candidates, we generated different SNP sets according to variable frequency cutoffs. By applying the PRSs to the validation set, we identified the optimal SNP set, which was then applied to a Greek nonalcoholic fatty liver disease (NAFLD) study., Results: Data from 3553 UK Biobank participants yielded 49 different SNP sets. After calculating the PRS on the validation set for every SNP set, an optimal PRS with 75 SNPs was selected (incremental R 2 = 0.025, p -value = 0.00145). Interestingly, 43 SNPs were successfully mapped to MASLD-related known genes. The selected PRS could predict traits, like LDL cholesterol and diastolic blood pressure in the UK Biobank, as also disease outcome in the Greek NAFLD study., Conclusions: Our findings provide strong evidence that PRS is a powerful prediction model for MASLD, while it can also be applied on populations of different ethnicity.

Obesity is a critical public health issue, necessitating effective weight loss interventions. While various dietary regimens have been explored, individual responses to interventions often vary. This study involved a 3-month dietary intervention aiming at assessing the role of macronutrient composition and the potential role of genetic predisposition in weight loss among Greek adults. This randomized clinical trial followed the CONSORT principles, recruiting 202 participants overall; 94 received a hypocaloric, high-protein diet and 108 received a high-carbohydrate, hypocaloric diet. Genetic predispositions were assessed through 10 target variants known for their BMI associations. Participants' weight and BMI values were recorded at baseline and post-intervention ( n = 202 at baseline, n = 84 post-intervention) and an imputation method was applied to account for the observed missing values. Participants experienced a statistically significant weight loss across all dietary regimens ( p < 0.001). Genetic analyses did not display statistically significant effects on weight loss. No significant differences in weight loss were observed between macronutrient groups, aligning with the POUNDS Lost and DIETFITS studies. This study underscores the importance of dietary interventions for weight loss and the potential contributions of genetic makeup. These findings contribute to obesity management within the Greek population and support the need for further research in personalized interventions.

Hypertension is a chronic, multifactorial disease, leading to high cardiovascular morbidity and mortality globally. Despite the advantages of pharmaceutical treatments, natural products have gained scientific interest due to their emerging phytotherapeutic properties. Chios mastic is a natural Greek product, consisting of bioactive compounds which modify microRNAs' (small, expression-regulating molecules) expression. In this study, we investigated the antihypertensive properties of Chios mastic through the assessment of miR-21 levels. Herein, plasma samples of 57 individuals with hypertension, recruited for the purposes of the HYPER-MASTIC study, were analyzed. This was a clinical trial with Chios mastic supplements in which the patients were divided into groups receiving high and low mastic doses and placebo supplements, respectively. miR-21 was significantly upregulated in patients compared to normotensive individuals. Mean changes in miR-21 levels were statistically significant, after adjusting for sex and age, between the placebo and low-dose group and between the low- and high-dose group. Post-intervention miR-21 levels were positively associated with night-time systolic blood pressure, pulse pressure, and central systolic mean arterial pressure and negatively associated with night-time pulse wave velocity in the low-dose group. Our findings suggest a potential implication of miR-21 in the association of Chios mastic with night-time blood pressure measurements.

Coronary artery disease (CAD) stands as the most predominant type of cardiovascular disease (CVD). Polygenic risk scores (PRSs) have become essential tools for quantifying genetic susceptibility, and researchers endeavor to improve their predictive precision. The aim of the present work is to assess the performance and the relative contribution of PRSs developed for CVD or CAD within a Greek population. The sample under study comprised 924 Greek individuals (390 cases with CAD and 534 controls) from the THISEAS study. Nine PRSs drawn from the PGS catalog were replicated and tested for CAD risk prediction. PRSs computations were performed in the R language, and snpStats was used to process genotypic data. Descriptive characteristics of the study were analyzed using the statistical software IBM SPSS Statistics v21.0. The effectiveness of each PRS was assessed using the PRS R 2 metric provided by PRSice2. Among nine PRSs, PGS000747 greatly increased the predictive value of primary CAD risk factors by 21.6% ( p -value = 2.63 × 10 -25 ). PGS000012 was associated with a modest increase in CAD risk by 2.2% ( p -value = 9.58 × 10 -4 ). The remarkable risk discrimination capability of PGS000747 stands out as the most noteworthy outcome of our study.

An ensemble of confounding factors, such as an unhealthy diet, obesity, physical inactivity, and smoking, have been linked to a lifestyle that increases one's susceptibility to chronic diseases and early mortality. The circulatory metabolome may provide a rational means of pinpointing the advent of metabolite variations that reflect an adherence to a lifestyle and are associated with the occurrence of chronic diseases. Data related to four major modifiable lifestyle factors, including adherence to the Mediterranean diet (estimated on MedDietScore), body mass index (BMI), smoking, and physical activity level (PAL), were used to create the lifestyle risk score (LS). The LS was further categorized into four groups, where a higher score group indicates a less healthy lifestyle. Drawing on this, we analyzed 223 NMR serum spectra, 89 MASLD patients and 134 controls; these were coupled to chemometrics to identify "key" features and understand the biological processes involved in specific lifestyles. The unsupervised analysis verified that lifestyle was the factor influencing the samples' differentiation, while the supervised analysis highlighted metabolic signatures. Τhe metabolic ratios of alanine/formic acid and leucine/formic acid, with AUROC > 0.8, may constitute discriminant indexes of lifestyle. On these grounds, this research contributed to understanding the impact of lifestyle on the circulatory metabolome and highlighted "prudent lifestyle" biomarkers.

Metabolic dysfunction-associated steatotic liver disease (MASLD), described as the most prominent cause of chronic liver disease worldwide, has emerged as a significant public health issue, posing a considerable challenge for most countries. Endocrine-disrupting chemicals (EDCs), commonly found in daily use items and foods, are able to interfere with nuclear receptors (NRs) and disturb hormonal signaling and mitochondrial function, leading, among other metabolic disorders, to MASLD. EDCs have also been proposed to cause transgenerationally inherited alterations leading to increased disease susceptibility. In this review, we are focusing on the most prominent linking pathways between EDCs and MASLD, their role in the induction of epigenetic transgenerational inheritance of the disease as well as up-to-date practices aimed at reducing their impact.

Introduction: Diet is one of the most important modifiable risk factors associated with cardiovascular health (CH). Research identifying dietary patterns (DPs) through data-driven analysis and reporting associations between DPs and coronary artery disease (CAD) outcomes is rather limited., Objective: The aim of the present report was to generate DPs through factor analysis (FA) and to examine their association with CAD risk., Methods: Participants ( n = 1017) consisted of cases diagnosed with CAD ( n = 356) and controls ( n = 661) drawn from the THISEAS study. Demographic, anthropometric and lifestyle data were collected. Dietary components were generated through FA. Logistic regression analysis was performed to estimate CAD relative risks., Results: FA generated seven dietary components, explaining 53.5% of the total variation in intake. The Western-type DP showed a modest significant association with CAD risk, after controlling for confounders (OR = 1.20; 95% CI = 1.09-1.32, p < 0.001). The vegetarian-type DP was not significantly associated with the likelihood of CAD (OR = 0.95; 95% CI = 0.84-1.04, p = 0.259)., Discussion: The Western-type DP was positively associated with CAD risk and the odds were further increased after controlling for confounders. This finding is in concordance with previously reported positive associations between Western patterns and CAD risk. Limited data exist regarding a posteriori DPs and their effect on CAD risk.

Objective: Obesity poses an increased risk for the onset of Nonalcoholic fatty liver disease (NAFLD). The influence of other factors, such as sex in the incidence and severity of this liver disease has not yet been fully elucidated. Thus, we aimed to identify the NAFLD serum metabolic signatures associated with sex in normal, overweight and obese patients and to associate the metabolite fluctuations across the increasing liver steatosis stages., Methods and Results: Using nuclear magnetic resonance (NMR) serum samples of 210 NAFLD cases and control individuals diagnosed with liver U/S, our untargeted metabolomics enquiry provided a sex distinct metabolic bouquet. Increased levels of alanine, histidine and tyrosine are associated with severity of NAFLD in both men and women. Moreover, higher serum concentrations of valine, aspartic acid and mannose were positively associated with the progression of NAFLD among the male subjects, while a negative association was observed with the levels of creatine, phosphorylcholine and acetic acid. On the other hand, glucose was positively associated with the progression of NAFLD among the female subjects, while levels of threonine were negatively related. Fluctuations in ketone bodies acetoacetate and acetone were also observed among the female subjects probing a significant reduction in the circulatory levels of the former in NAFLD cases. A complex glycine response to hepatic steatosis of the female subjects deserves further investigation., Conclusion: Results of this study aspire to address the paucity of data on sex differences regarding NAFLD pathogenesis. Targeted circulatory metabolome measurements could be used as diagnostic markers for the distinct stages of NAFLD in each sex and eventually aid in the development of novel sex-related therapeutic options., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fotakis, Kalafati, Amanatidou, Andreou, Matzapetakis, Kafyra, Varlamis, Zervou and Dedoussis.)

Nutrition therapy aims to prevent weight loss and its health consequences in patients with cancer. The aim of this study was to assess Greek patients' adherence to the ESPEN guidelines for oncology patients and its prospective effect on their body weight (BW) and nutritional status. In total, 152 patients with cancer were recruited from the Attikon University Hospital, Greece, and provided data in 2019 (baseline) and 2020 (follow-up) (drop-out rate = 28.3%). Nutritional status was assessed with the PG-SGA questionnaire. Patients were categorized based on whether they adhered at least to the minimum ESPEN-recommended intakes of energy (≥25 kcal/kg/day) or protein (≥1.0 g/kg/day) or not. On average, patients did not adhere to ESPEN guidelines for energy and protein intake. Most patients meeting the minimum recommendations had an improvement of their nutritional status at follow-up and increased their BW compared to those not meeting them. All patients with head, neck, and spinal cancer who met the minimum recommendations for energy intake improved their nutritional status at follow-up. This study showed that consuming at least the minimum amounts of protein and energy recommended by ESPEN may prevent from weight loss and improve nutritional status; however, the exact amounts need to be personalized.

It is well acknowledged that most of the modifiable risk factors for Cardiovascular Diseases (CVDs) can be averted through lifestyle modifications beyond medication adherence. This review aims to critically evaluate the cardiometabolic (CM) patient-related factors that influence the adherence to lifestyle changes studied alone and/or in combination with medication. A comprehensive literature search of PubMed articles from 2000 to 2023 retrieved 379 articles. After removing the articles which were not relevant, a total of 28 cross-sectional studies was chosen (12 qualitative, and 16 quantitative). The findings confirmed that five groups of factors influence patients' adherence to overall treatment: (1) health beliefs, knowledge, and perceptions regarding the risks and challenges of disease and medication intake along with adherence process perceptions; (2) self-concept; (3) emotions; (4) patient-healthcare providers relationship/communication and (5) social and cultural interactions. It is worth mentioning that cultural issues, such as culinary particularities, ethnic identity, social life as well as patients' skills and abilities, play a profound role in the effectiveness of the recommended lifestyle modifications beyond the aforementioned common factors. The need for clear-cut culturally adapted guidelines along with personalized advice from physicians is imperative as it could improve patients' self-efficacy. These socio-psychological factors should be seriously considered as a means to increase the effectiveness of future community prevention programs.

Previous research has allowed the identification of variants related to the vascular endothelial growth factor-A (VEGF-A) and their association with anthropometric, lipidemic and glycemic indices. The present study examined potential relations between key VEGF-A-related single-nucleotide polymorphisms (SNPs), cardiometabolic parameters and dietary habits in an adolescent cohort. Cross-sectional analyses were conducted using baseline data from 766 participants of the Greek TEENAGE study. Eleven VEGF-A-related SNPs were examined for associations with cardiometabolic indices through multivariate linear regressions after adjusting for confounding factors. A 9-SNP unweighted genetic risk score (uGRS) for increased VEGF-A levels was constructed to examine associations and the effect of its interactions with previously extracted dietary patterns for the cohort. Two variants (rs4416670, rs7043199) displayed significant associations ( p -values < 0.005) with the logarithms of systolic and diastolic blood pressure (logSBP and logDBP). The uGRS was significantly associated with higher values of the logarithm of Body Mass Index (logBMI) and logSBP ( p -values < 0.05). Interactions between the uGRS and specific dietary patterns were related to higher logDBP and logGlucose ( p -values < 0.01). The present analyses constitute the first-ever attempt to investigate the influence of VEGF-A-related variants on teenage cardiometabolic determinants, unveiling several associations and the modifying effect of diet.

The aim of the present work was two-fold. Firstly, to evaluate the association between the consumption of ultra-processed beverages (UPB) on preadolescents' likelihood of being obese. Secondly, to investigate the potential impact of family and school environmental stressors on this unhealthy lifestyle habit. A cross-sectional study was conducted among 1718 Greek preadolescents and their parents, during the school years 2014 to 2016. Parental and child characteristics were collected anonymously, through self-administered and validated questionnaires. Among others, UPB consumption (soft and flavored drinks) was recorded, classifying children as low, moderate, or high consumers, while anthropometric characteristics [height, body weight, Body Mass Index (BMI)] were also recorded. Almost seven out of ten preadolescents were classified as at least moderate UPB consumers, while approximately three out of ten were classified as high UPB consumers. Higher UPB consumption was associated with significantly higher levels of BMI, while preadolescents living in a more stressful family and school environment were found to consume significantly higher amounts of UPB. Stakeholders should implement programs that raise awareness among parents and teachers about the sources of stress in preadolescence as a potential "triggering factor" of unhealthy dietary preferences.

The epidemic prevalence of non-alcoholic fatty liver disease (NAFLD), despite extensive research in the field, underlines the importance of focusing on personalized therapeutic approaches. However, nutrigenetic effects on NAFLD are poorly investigated. To this end, we aimed to explore potential gene-dietary pattern interactions in a NAFLD case-control study. The disease was diagnosed with liver ultrasound and blood collection was performed after an overnight fast. Adherence to four a posteriori, data-driven, dietary patterns was used to investigate interactions with PNPLA3-rs738409, TM6SF2-rs58542926, MBOAT7-rs641738, and GCKR-rs738409 in disease and related traits. IBM SPSS Statistics/v21.0 and Plink/v1.07 were used for statistical analyses. The sample consisted of 351 Caucasian individuals. PNPLA3-rs738409 was positively associated with disease odds (OR = 1.575, p = 0.012) and GCKR-rs738409 with lnC-reactive protein (CRP) (beta = 0.098, p = 0.003) and Fatty Liver Index (FLI) levels (beta = 5.011, p = 0.007). The protective effect of a "Prudent" dietary pattern on serum triglyceride (TG) levels in this sample was significantly modified by TM6SF2-rs58542926 ( p interaction = 0.007). TM6SF2-rs58542926 carriers may not benefit from a diet rich in unsaturated fatty acids and carbohydrates in regard to TG levels, a commonly elevated feature in NAFLD patients.

Quantifying the role of genetics via construction of polygenic risk scores (PRSs) is deemed a resourceful tool to enable and promote effective obesity prevention strategies. The present paper proposes a novel methodology for PRS extraction and presents the first PRS for body mass index (BMI) in a Greek population. A novel pipeline for PRS derivation was used to analyze genetic data from a unified database of three cohorts of Greek adults. The pipeline spans various steps of the process, from iterative dataset splitting to training and test partitions, calculation of summary statistics and PRS extraction, up to PRS aggregation and stabilization, achieving higher evaluation metrics. Using data from 2185 participants, implementation of the pipeline enabled consecutive repetitions in splitting training and testing samples and resulted in a 343-single nucleotide polymorphism PRS yielding an R 2 = 0.3241 (beta = 1.011, p -value = 4 × 10 -193 ) for BMI. PRS-included variants displayed a variety of associations with known traits (i.e., blood cell count, gut microbiome, lifestyle parameters). The proposed methodology led to creation of the first-ever PRS for BMI in Greek adults and aims at promoting a facilitating approach to reliable PRS development and integration in healthcare practice.

Cancer patients are at risk of malnutrition, which influences their functional status, mental health (MH), and quality of life (QoL). This study aimed to examine the associations between nutritional status, functional capacity, and aspects of QoL in cancer patients, as well as the potential mediating role of depression and anxiety in these associations. Patients with various types of cancer ( n  = 152) were recruited from the Attikon University Hospital, Greece. Validated questionnaires were used to assess nutritional status (PG-SGA), QoL (SF-36 and EQ-5D-3L), functional capacity (ECOG), depression, and anxiety (HADS and BEDS). Handgrip strength (HGS) was also measured. Poor nutritional status was inversely associated with functional capacity, QoL, depression, and anxiety, after adjusting for confounding factors (all P  ≤ 0.05). Mediation analysis indicated a significant indirect effect of nutritional status on various parameters of functional capacity and QoL through depression and anxiety, after adjusting for age and sex. Mediated proportion ranged from 26.3-34% to 23.1-82.8% for functional capacity and QoL, respectively. A significant proportion of the effect of nutritional status on QoL and functional capacity can be partly attributed to psychological effects, highlighting the significance of integrating all aforementioned aspects in the nutritional intervention for cancer patients.

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes 1 . Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel 2 ) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries., (© 2022. The Author(s).)

Whereas the etiology of non-alcoholic fatty liver disease (NAFLD) is complex, the role of nutrition as a causing and preventive factor is not fully explored. The aim of this study is to associate dietary patterns with magnetic resonance imaging (MRI) parameters in a European population (Greece, Italy, and Serbia) affected by NAFLD. For the first time, iron-corrected T1 (cT1), proton density fat fraction (PDFF), and the liver inflammation fibrosis score (LIF) were examined in relation to diet. A total of 97 obese patients with NAFLD from the MAST4HEALTH study were included in the analysis. A validated semi-quantitative food frequency questionnaire (FFQ) was used to assess the quality of diet and food combinations. Other variables investigated include anthropometric measurements, total type 2 diabetes risk, physical activity level (PAL), and smoking status. Principal component analysis (PCA) was performed to identify dietary patterns. Six dietary patterns were identified, namely "High-Sugar", "Prudent", "Western", "High-Fat and Salt", "Plant-Based", and "Low-Fat Dairy and Poultry". The "Western" pattern was positively associated with cT1 in the unadjusted model (beta: 0.020, p -value: 0.025) and even after adjusting for age, sex, body mass index (BMI), PAL, smoking, the center of the study, and the other five dietary patterns (beta: 0.024, p -value: 0.020). On the contrary, compared with low-intake patients, those with medium intake of the "Low-Fat Dairy and Poultry" pattern were associated with lower values of cT1, PDFF, and LIF. However, patients with a "Low-Fat Dairy and Poultry" dietary pattern were negatively associated with MRI parameters (cT1: beta: -0.052, p -value: 0.046, PDFF: beta: -0.448, p -value: 0.030, LIF: beta: -0.408, p -value: 0.025). Our findings indicate several associations between MRI parameters and dietary patterns in NAFLD patients, highlighting the importance of diet in NAFLD.

Background: Dietary and lifestyle habits constitute a significant contributing factor in the formation of anthropometric and biochemical characteristics of overweight and obese populations. The iMPROVE study recruited overweight and obese Greek adults and investigated the effect of gene-diet interactions on weight management when adhering to a six-month, randomized nutritional trial including two hypocaloric diets of different macronutrient content. The present paper displays the design of the intervention and the baseline findings of the participants' dietary habits and their baseline anthropometric and biochemical characteristics., Methods: Baseline available data for 202 participants were analyzed and patterns were extracted via principal component analysis (PCA) on 69-item Food-Frequency Questionnaires (FFQ). Relationships with indices at baseline were investigated by multivariate linear regressions. A Lifestyle Index of five variables was further constructed., Results: PCA provided 5 dietary patterns. The "Mixed" pattern displayed positive associations with logBMI and logVisceral fat, whereas the "Traditional, vegetarian-alike" pattern was nominally, negatively associated with body and visceral fat, but positively associated with HDL levels. The Lifestyle Index displayed protective effects in the formation of logBMI and logGlucose levels., Conclusions: Dietary patterns and a Lifestyle Index in overweight and obese, Greek adults highlighted associations between diet, lifestyle, and anthropometric and biochemical indices.

The present study sought to retrospectively investigate the dietary habits of two adolescent, European populations from the cross-sectional Greek TEENAGE Study and French STANISLAS Family Study. We aimed to explore the relation between the populations' dietary patterns and blood pressure, glycemic and lipidemic profile. Dietary patterns were extracted via Principal Component Analysis (PCA), based on data collected from two 24 h dietary recalls for the TEENAGE study and a 3-day food consumption diary for the STANISLAS study. Multiple linear regressions and mixed models analyses, adjusting for confounding factors, were employed to investigate potential associations. A total of 766 Greek teenagers and 287 French teenagers, were included in analyses. Five dietary patterns were extracted for each population accounting for 49.35% and 46.69% of their respective total variance, with similarities regarding the consumption of specific food groups (i.e., western-type foods). In the TEENAGE Study, the "chicken and sugars" pattern was associated with lower CRP levels, after adjusting for confounding factors ( p -value < 0.01). The "high protein and animal fat" dietary pattern of the STANISLAS Family Study was related to higher BMI ( p -value < 0.01) and higher triglycerides levels ( p -value < 0.01). Our findings summarize the dietary habits of two teenage, European populations and their associations with cardiometabolic risk factors.

Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P < 1 × 10 -6 ) associated with intake of any macronutrient in 91,114 European ancestry participants. Four loci replicated and reached genome-wide significance in a combined meta-analysis including 123,659 European descent participants, unraveling two novel loci; a common variant in RARB locus for carbohydrate intake and a rare variant in DRAM1 locus for protein intake, and corroborating earlier FGF21 and FTO findings. In additional analysis of 144,770 participants from the UK Biobank, all identified associations from the two-stage analysis were confirmed except for DRAM1. Identified loci might have implications in brain and adipose tissue biology and have clinical impact in obesity-related phenotypes. Our findings provide new insight into biological functions related to macronutrient intake.

Diet is a modifiable key factor targeted in prevention and management of nonalcoholic fatty liver disease (NAFLD). The aim was to study the effect of Mediterranean Diet (MedDiet) on clinical, biochemical, and inflammatory profile in NAFLD patients with simple steatosis. Potential associations of signal transducer and activator of transcription 3 (STAT3) rs2293152 genotype to diet composition and patients' profile were investigated. In this nonrandomized, open-label, 24-week prospective intervention study, 44 untreated NAFLD patients with nonsignificant fibrosis received nutritional counsel to increase adherence to MedDiet. Adherence to MedDiet was estimated with MedDietScore. Furthermore, we genotyped STAT3 rs2293152 single nucleotide polymorphism and performed clinical and inflammatory measurements. In all patients, MedDietScore increased and anthropometric indices improved, whereas liver imaging, liver fibrosis score, blood pressure, fasting glucose, glycated hemoglobin (HbA1c), C-reactive protein (CRP), visfatin, and oxidized low-density lipoprotein levels were also significantly ameliorated compared with baseline ( P  < .05). No association of STAT3 polymorphism with diet composition was found. Comparisons of mean differences between G- and C-carriers at the end point of the trial showed that only visfatin was significantly associated with the STAT3 genotype (-0.0 ± 4.6 vs. -4.2 ± 3.9, P  = .04, respectively). Carrying the G-allele was associated with an increase of the visfatin levels (3.4 ± 1.5 ng/mL, P  = .028). Our results show amelioration of clinical, biochemical, and inflammatory biomarkers in NAFLD patients in response to MedDiet. STAT3 rs2293152 G-carriers experienced more beneficial changes at the end of the intervention compared with baseline. An association between visfatin levels and STAT3 genotype has been shown for the first time.

Purpose: Non-alcoholic fatty liver disease (NAFLD) is a complex disease, resulting from a variety of genetic and environmental factors. The aim of this case-control study was to evaluate the effect of selected genetic polymorphisms, nutrition aspects and their interaction on the risk of NAFLD., Methods: The sample consisted of 134 patients with NAFLD and 217 controls. Disease was diagnosed by liver ultrasound and volunteers were clinically and nutritionally assessed. Food groups were extracted from a 172 food-item FFQ questionnaire. Three genetic polymorphisms were assessed: PNPLA3 rs738409, TM6SF2 rs58542926 and GCKR rs780094., Results: We replicated the effect of previously reported risk factors for NAFLD, such as elevated liver enzymes, obesity and metabolic syndrome. Food groups rich in simple sugars, fat and especially saturated fat were positively associated with NAFLD risk, whereas food groups rich in polyunsaturated fatty acids were reversely associated with the possibility of developing the disease (p < 0.05). Only the PNPLA3 genetic variant was statistically significantly associated with the disease (p additive  = 0.015). However, it was found that a one-portion increase in fish intake increased the risk of NAFLD in carriers of the risk allele of TM6SF2 rs58542926 polymorphism compared to non-carriers, after adjusting for age, gender, energy intake, pack-years, PAL, TM6SF2 genotype and fish consumption (OR dominant  = 1.503, 95% CI 1.094-2.064)., Conclusions: Fish intake exerts an additive effect on NAFLD risk for carriers of the TM6SF2 polymorphism. This novel finding provides further rationale on the need for personalized nutritional advice, based on the genetic background of NAFLD patients.

Objective: The aim of this study was to test the hypothesis that posteriori-derived dietary patterns of a Greek sample are associated with the odds for non-alcoholic fatty liver disease (NAFLD) and common NAFLD-related biomarkers., Methods: We recruited 351 individuals (134 NAFLD patients, 217 controls). NAFLD was diagnosed with abdominal ultrasound. Dietary intake data were collected through a semi-quantitative food frequency questionnaire of 172 items and dietary patterns were derived by factor analysis. Consumption of dietary patterns was divided into quartiles. Multivariate logistic and linear regression models were applied to investigate associations of dietary patterns with NAFLD odds and common NAFLD-associated biomarkers., Results: Four dietary patterns were identified. Adherence to the fast food-type dietary pattern was independently associated with higher odds for NAFLD. However, results were statistically significant only for the highest versus the lowest consumption (odds ratio, 3.9; P = 0.003). On the contrary, individuals in the second quartile of the unsaturated fatty acid dietary pattern had 55.7% reduced odds of developing NAFLD than those in the first quartile after adjusting for age, sex, energy intake, physical activity level, pack-years smoked, education years, and presence of metabolic syndrome (P = 0.039). The fast food-type pattern was further associated with higher levels of C-reactive protein and uric acid and the unsaturated fatty acid pattern with reduced levels of insulin and homeostatic model assessment of insulin resistance (P < 0.05). The prudent dietary pattern was associated with decreased triacylglycerol and uric acid levels (β = -5.960; P = 0.037 and β = -0.153; P = 0.035, respectively)., Conclusion: This is the first study to indicate associations of dietary patterns with NAFLD in a European population., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of metabolic syndrome. Its global prevalence is estimated between 25 and 45%, occurring mainly in overweight individuals with unhealthy dietary habits and low levels of physical activity. Many studies have investigated the association of trace elements with liver diseases, though not with NAFLD. In this work, we investigated trace element levels in plasma of patients and not-patients and their possible association with various stages of the disease. Inductively coupled plasma mass spectrometry (ICP-MS) was employed for the determination of As, Ba, Cd, Co, Cs, Cu, Fe, Rb, Sr, Tl, and Zn in the plasma of 189 free-living residents of Athens, Greece, either healthy or patients with mild, moderate, or severe NAFLD. The disease was diagnosed by abdominal ultrasound; blood samples were analyzed for total, HDL and LDL cholesterol, triglycerides, fasting glucose, fasting insulin, and liver enzymes, namely aspartate aminotransferase (AST), alanine transaminase (ALT), and γ-glutamyltransferase (Gamma-GT); insulin resistance was determined by the homeostatic model assessment (HOMA-IR). Zinc exhibited a statistically significant negative association with the severity of the disease, while cesium showed a statistically significant positive association. Moreover, thallium and iron were inversely associated with insulin levels. Trace element determination in plasma could be useful for establishing relationships with NAFLD status of patients. Further research is required for the verification and interpretation of these findings.

Aim: To investigate the association between GCKR gene and nutritional treatment in NAFLD-related biomarkers., Methods: This was an open-label and single-arm clinical trial in 44 overweight or obese adults with NAFLD receiving nutritional counseling for 6 months. Nutritional data, MedDietScore, clinical, biochemical, inflammatory and oxidative stress biomarkers were evaluated before and after intervention. Further, we genotyped GCKR rs1260326 and in T-allele carriers and non-Τ-carriers we assessed associations between the GCKR variant and nutritional counseling related to change in all biomarkers evaluated., Results: Anthropometric measurements were significantly reduced after the end of the intervention in patients assigned to nutritional counseling. Liver imaging and fibrosis were significantly improved. GCKR rs1260326 T-allele frequency was 46.7%. T-carriers responded better to nutritional counseling regarding fasting blood glucose levels (mean 6-0 change = -4.94 mg/dL (±9.33), p = 0.005), whereas non-T-carriers did not benefit from the intervention regarding glucose. On the other hand, levels of oxLDL decreased in the non-T-carriers group after the intervention, but not in T-carriers., Conclusions: Our results show that GCKR rs1260326 T-allele is associated with better response of NAFLD patients to nutritional treatment regarding fasting blood glucose, but not oxLDL levels. Despite this important finding in the field of nutrigenetics, it is tricky to generalize this effect unless larger studies are conducted.

Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.

Objective: The aims of the current report are to present the demographic characteristics, clinical characteristics/biochemical indices and lifestyle habits of the population and to explore the potential association of exclusive olive oil consumption, in relation to lifestyle factors, with coronary artery disease risk., Design: Demographic, lifestyle, dietary and biochemical variables were recorded. Logistic regression analysis was performed in order to estimate the relative risks of developing coronary artery disease., Setting: The Hellenic study of Interactions between Single nucleotide polymorphisms and Eating in Atherosclerosis Susceptibility (THISEAS), a medical centre-based case-control study conducted in Greek adults., Subjects: We consecutively enrolled 1221 adult patients with coronary artery disease and 1344 adult controls., Results: A higher prevalence of the conventional established risk factors was observed in cases than in controls. Physical activity level was higher in controls (1·4 (sd 0·2) than in cases (1·3 (sd 0·3); P<0·001). Regarding current and ex-smokers, the case group reported almost double the pack-years of the control group (54·6 (sd 42·8) v. 28·3 (sd 26·3), respectively; P<0·001). Exclusive olive oil consumption was associated with 37 % lower likelihood of developing coronary artery disease, even after taking into account adherence to the Mediterranean diet (OR=0·63; 95 % CI 0·42, 0·93; P=0·02)., Conclusions: Exclusive olive oil consumption was associated with lower risk of coronary artery disease, even after adjusting for adoption of an overall healthy dietary pattern such as the Mediterranean diet.

Background: Recent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown., Objective: We investigated the associations of meat intake and the interaction of meat with genotype on fasting glucose and insulin concentrations in Caucasians free of diabetes mellitus., Design: Fourteen studies that are part of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium participated in the analysis. Data were provided for up to 50,345 participants. Using linear regression within studies and a fixed-effects meta-analysis across studies, we examined 1) the associations of processed meat and unprocessed red meat intake with fasting glucose and insulin concentrations; and 2) the interactions of processed meat and unprocessed red meat with genetic risk score related to fasting glucose or insulin resistance on fasting glucose and insulin concentrations., Results: Processed meat was associated with higher fasting glucose, and unprocessed red meat was associated with both higher fasting glucose and fasting insulin concentrations after adjustment for potential confounders [not including body mass index (BMI)]. For every additional 50-g serving of processed meat per day, fasting glucose was 0.021 mmol/L (95% CI: 0.011, 0.030 mmol/L) higher. Every additional 100-g serving of unprocessed red meat per day was associated with a 0.037-mmol/L (95% CI: 0.023, 0.051-mmol/L) higher fasting glucose concentration and a 0.049-ln-pmol/L (95% CI: 0.035, 0.063-ln-pmol/L) higher fasting insulin concentration. After additional adjustment for BMI, observed associations were attenuated and no longer statistically significant. The association of processed meat and fasting insulin did not reach statistical significance after correction for multiple comparisons. Observed associations were not modified by genetic loci known to influence fasting glucose or insulin resistance., Conclusion: The association of higher fasting glucose and insulin concentrations with meat consumption was not modified by an index of glucose- and insulin-related single-nucleotide polymorphisms. Six of the participating studies are registered at clinicaltrials.gov as NCT0000513 (Atherosclerosis Risk in Communities), NCT00149435 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetics of Lipid Lowering Drugs and Diet Network), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis)., (© 2015 American Society for Nutrition.)

Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjusted WHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjusted WHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance., (© The Author 2015. Published by Oxford University Press.)

Objective: Common circadian-related gene variants associate with increased risk for metabolic alterations including type 2 diabetes. However, little is known about whether diet and sleep could modify associations between circadian-related variants (CLOCK-rs1801260, CRY2-rs11605924, MTNR1B-rs1387153, MTNR1B-rs10830963, NR1D1-rs2314339) and cardiometabolic traits (fasting glucose [FG], HOMA-insulin resistance, BMI, waist circumference, and HDL-cholesterol) to facilitate personalized recommendations., Research Design and Methods: We conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations and interactions between dietary intake/sleep duration and selected variants on cardiometabolic traits from 15 cohort studies including up to 28,190 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium., Results: We observed significant associations between relative macronutrient intakes and glycemic traits and short sleep duration (<7 h) and higher FG and replicated known MTNR1B associations with glycemic traits. No interactions were evident after accounting for multiple comparisons. However, we observed nominally significant interactions (all P < 0.01) between carbohydrate intake and MTNR1B-rs1387153 for FG with a 0.003 mmol/L higher FG with each additional 1% carbohydrate intake in the presence of the T allele, between sleep duration and CRY2-rs11605924 for HDL-cholesterol with a 0.010 mmol/L higher HDL-cholesterol with each additional hour of sleep in the presence of the A allele, and between long sleep duration (≥9 h) and MTNR1B-rs1387153 for BMI with a 0.60 kg/m(2) higher BMI with long sleep duration in the presence of the T allele relative to normal sleep duration (≥7 to <9 h)., Conclusions: Our results suggest that lower carbohydrate intake and normal sleep duration may ameliorate cardiometabolic abnormalities conferred by common circadian-related genetic variants. Until further mechanistic examination of the nominally significant interactions is conducted, recommendations applicable to the general population regarding diet—specifically higher carbohydrate and lower fat composition—and normal sleep duration should continue to be emphasized among individuals with the investigated circadian-related gene variants., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Background: Short sleep duration has been associated with greater risks of obesity, hypertension, diabetes, and cardiovascular disease. Also, common genetic variants in the human Circadian Locomotor Output Cycles Kaput (CLOCK) show associations with ghrelin and total energy intake., Objectives: We examined associations between habitual sleep duration, body mass index (BMI), and macronutrient intake and assessed whether CLOCK variants modify these associations., Design: We conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations of sleep duration and BMI and macronutrient intake as percentages of total energy as well as interactions with CLOCK variants from 9 cohort studies including up to 14,906 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium., Results: We observed a significant association between sleep duration and lower BMI (β ± SE = 0.16 ± 0.04, P < 0.0001) in the overall sample; however, associations between sleep duration and relative macronutrient intake were evident in age- and sex-stratified analyses only. We observed a significant association between sleep duration and lower saturated fatty acid intake in younger (aged 20-64 y) adults (men: 0.11 ± 0.06%, P = 0.03; women: 0.10 ± 0.05%, P = 0.04) and with lower carbohydrate (-0.31 ± 0.12%, P < 0.01), higher total fat (0.18 ± 0.09%, P = 0.05), and higher PUFA (0.05 ± 0.02%, P = 0.02) intakes in older (aged 65-80 y) women. In addition, the following 2 nominally significant interactions were observed: between sleep duration and rs12649507 on PUFA intake and between sleep duration and rs6858749 on protein intake., Conclusions: Our results indicate that longer habitual sleep duration is associated with lower BMI and age- and sex-specific favorable dietary behaviors. Differences in the relative intake of specific macronutrients associated with short sleep duration could, at least in part, explain previously reported associations between short sleep duration and chronic metabolic abnormalities. In addition, the influence of obesity-associated CLOCK variants on the association between sleep duration and macronutrient intake suggests that longer habitual sleep duration could ameliorate the genetic predisposition to obesity via a favorable dietary profile., (© 2015 American Society for Nutrition.)

Background: Macronutrient intake varies substantially between individuals, and there is evidence that this variation is partly accounted for by genetic variants., Objective: The objective of the study was to identify common genetic variants that are associated with macronutrient intake., Design: We performed 2-stage genome-wide association (GWA) meta-analysis of macronutrient intake in populations of European descent. Macronutrients were assessed by using food-frequency questionnaires and analyzed as percentages of total energy consumption from total fat, protein, and carbohydrate. From the discovery GWA (n = 38,360), 35 independent loci associated with macronutrient intake at P < 5 × 10(-6) were identified and taken forward to replication in 3 additional cohorts (n = 33,533) from the DietGen Consortium. For one locus, fat mass obesity-associated protein (FTO), cohorts with Illumina MetaboChip genotype data (n = 7724) provided additional replication data., Results: A variant in the chromosome 19 locus (rs838145) was associated with higher carbohydrate (β ± SE: 0.25 ± 0.04%; P = 1.68 × 10(-8)) and lower fat (β ± SE: -0.21 ± 0.04%; P = 1.57 × 10(-9)) consumption. A candidate gene in this region, fibroblast growth factor 21 (FGF21), encodes a fibroblast growth factor involved in glucose and lipid metabolism. The variants in this locus were associated with circulating FGF21 protein concentrations (P < 0.05) but not mRNA concentrations in blood or brain. The body mass index (BMI)-increasing allele of the FTO variant (rs1421085) was associated with higher protein intake (β ± SE: 0.10 ± 0.02%; P = 9.96 × 10(-10)), independent of BMI (after adjustment for BMI, β ± SE: 0.08 ± 0.02%; P = 3.15 × 10(-7))., Conclusion: Our results indicate that variants in genes involved in nutrient metabolism and obesity are associated with macronutrient consumption in humans. Trials related to this study were registered at clinicaltrials.gov as NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetic and Environmental Determinants of Triglycerides), NCT01331512 (InCHIANTI Study), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).