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Food-drug interactions (FDIs) occur when a food item alters the pharmacokinetics or pharmacodynamics of a drug. FDIs can be clinically relevant, as they can hamper or enhance the therapeutic effects of a drug and impact both their efficacy and their safety. However, knowledge of FDIs in clinical practice is limited. This is partially due to the lack of resources focused on FDIs. Here, we describe FooDrugs, a database that centralizes FDI knowledge retrieved from two different approaches: a natural processing language pipeline that extracts potential FDIs from scientific documents and clinical trials and a molecular similarity approach based on the comparison of gene expression alterations caused by foods and drugs. FooDrugs database stores a total of 3 430 062 potential FDIs, with 1 108 429 retrieved from scientific documents and 2 321 633 inferred from molecular data. This resource aims to provide researchers and clinicians with a centralized repository for potential FDI information that is free and easy to use. Database URL: https://zenodo.org/records/8192515 Database DOI: https://doi.org/10.5281/zenodo.6638469.
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Interações Alimento-Droga , Idioma , Bases de Dados Factuais , Regulação da Expressão Gênica , ConhecimentoRESUMO
The increasing prevalence of diet-related diseases calls for an improvement in nutritional advice. Personalized nutrition aims to solve this problem by adapting dietary and lifestyle guidelines to the unique circumstances of each individual. With the latest advances in technology and data science, researchers can now automatically collect and analyze large amounts of data from a variety of sources, including wearable and smart devices. By combining these diverse data, more comprehensive insights of the human body and its diseases can be achieved. However, there are still major challenges to overcome, including the need for more robust data and standardization of methodologies for better subject monitoring and assessment. Here, we present the AI4Food database (AI4FoodDB), which gathers data from a nutritional weight loss intervention monitoring 100 overweight and obese participants during 1 month. Data acquisition involved manual traditional approaches, novel digital methods and the collection of biological samples, obtaining: (i) biological samples at the beginning and the end of the intervention, (ii) anthropometric measurements every 2 weeks, (iii) lifestyle and nutritional questionnaires at two different time points and (iv) continuous digital measurements for 2 weeks. To the best of our knowledge, AI4FoodDB is the first public database that centralizes food images, wearable sensors, validated questionnaires and biological samples from the same intervention. AI4FoodDB thus has immense potential for fostering the advancement of automatic and novel artificial intelligence techniques in the field of personalized care. Moreover, the collected information will yield valuable insights into the relationships between different variables and health outcomes, allowing researchers to generate and test new hypotheses, identify novel biomarkers and digital endpoints, and explore how different lifestyle, biological and digital factors impact health. The aim of this article is to describe the datasets included in AI4FoodDB and to outline the potential that they hold for precision health research. Database URL https://github.com/AI4Food/AI4FoodDB.
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Telemedicina , Dispositivos Eletrônicos Vestíveis , Humanos , Inteligência Artificial , Dieta , Estilo de VidaRESUMO
Background: Online health data collection has gained a reputation over the last years to record and process information about health issues for implementing digital health. Objective: The research aim was to appraise two online methods (open and rewarded) to collect information about HRQoL and nutritional well-being and to compare the results between both surveyed populations. Methods: This cross-sectional study is framed on the NUTRiMDEA project. Online data through two different web-based methods (open survey and rewarded survey) were retrieved to assemble data related to sociodemographic, lifestyle (diet, physical activity and sleep patterns) and general health aspects, as well as HRQoL by an evidence-based form such as the SF-12 questionnaire, the IPAQ survey, and MEDAS-14, participants were adults (>18 years old). Results: Overall, 17,332 participants responded to the open survey (OS, n = 11,883) or the rewarded survey (RS, n = 5449). About 65.1% of the participants were female, while the mean age was in the range of 40-70 years. There were significant differences (p < 0.05) between surveyed populations in sociodemographic, lifestyle (diet and physical activity), health and HRQoL data. Conclusions: This investigation implemented an evidence-based online questionnaire that collected demographic, lifestyle factors, phenotypic and health-related aspects as well as compared differential outcomes in HRQoL and nutritional/lifestyle well-being depending on the online mode data collection. Findings demonstrated dissimilarities in most aspects of health, HRQoL, dietary intake and physical activity records between both populations. Overall, OS sample was characterized as a healthier population with superior lifestyle habits than RS participants.
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BACKGROUND: Overweight and obesity are defined by an anomalous or excessive fat accumulation that may compromise health. To find single-nucleotide polymorphisms (SNPs) influencing metabolic phenotypes associated with the obesity state, we analyze multiple anthropometric and clinical parameters in a cohort of 790 healthy volunteers and study potential associations with 48 manually curated SNPs, in metabolic genes functionally associated with the mechanistic target of rapamycin (mTOR) pathway. RESULTS: We identify and validate rs2291007 within a conserved region in the 3'UTR of folliculin-interacting protein FNIP2 that correlates with multiple leanness parameters. The T-to-C variant represents the major allele in Europeans and disrupts an ancestral target sequence of the miRNA miR-181b-5p, thus resulting in increased FNIP2 mRNA levels in cancer cell lines and in peripheral blood from carriers of the C allele. Because the miRNA binding site is conserved across vertebrates, we engineered the T-to-C substitution in the endogenous Fnip2 allele in mice. Primary cells derived from Fnip2 C/C mice show increased mRNA stability, and more importantly, Fnip2 C/C mice replicate the decreased adiposity and increased leanness observed in human volunteers. Finally, expression levels of FNIP2 in both human samples and mice negatively associate with leanness parameters, and moreover, are the most important contributor in a multifactorial model of body mass index prediction. CONCLUSIONS: We propose that rs2291007 influences human leanness through an evolutionarily conserved modulation of FNIP2 mRNA levels.
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MicroRNAs , Sobrepeso , Humanos , Animais , Camundongos , Regiões 3' não Traduzidas , Sobrepeso/genética , Magreza/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Obesidade/genética , Proteínas de Transporte/metabolismoRESUMO
Approximately 25% of colorectal cancer (CRC) patients experience systemic metastases, with the most frequent target organs being the liver and lung. Metabolic reprogramming has been recognized as one of the hallmarks of cancer. Here, metabolic and functional differences between two CRC cells with different metastatic organotropisms (metastatic KM12SM CRC cells to the liver and KM12L4a to the lung when injected in the spleen and in the tail vein of mice) were analysed in comparison to their parental non-metastatic isogenic KM12C cells, for a subsequent investigation of identified metabolic targets in CRC patients. Meta-analysis from proteomic and transcriptomic data deposited in databases, qPCR, WB, in vitro cell-based assays, and in vivo experiments were used to survey for metabolic alterations contributing to their different organotropism and for the subsequent analysis of identified metabolic markers in CRC patients. Although no changes in cell proliferation were observed between metastatic cells, KM12SM cells were highly dependent on oxidative phosphorylation at mitochondria, whereas KM12L4a cells were characterized by being more energetically efficient with lower basal respiration levels and a better redox management. Lipid metabolism-related targets were found altered in both cell lines, including LDLR, CD36, FABP4, SCD, AGPAT1, and FASN, which were also associated with the prognosis of CRC patients. Moreover, CD36 association with lung metastatic tropism of CRC cells was validated in vivo. Altogether, our results suggest that LDLR, CD36, FABP4, SCD, FASN, LPL, and APOA1 metabolic targets are associated with CRC metastatic tropism to the liver or lung. These features exemplify specific metabolic adaptations for invasive cancer cells which stem at the primary tumour.
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The pandemic burden caused by the SARS-CoV-2 coronavirus constitutes a global public health emergency. Increasing understanding about predisposing factors to infection and severity is now a priority. Genetic, metabolic, and environmental factors can play a crucial role in the course and clinical outcome of COVID-19. We aimed to investigate the putative relationship between genetic factors associated to obesity, metabolism and lifestyle, and the presence and severity of SARS-CoV-2 infection. A total of 249 volunteers (178 women and 71 men, with mean and ± SD age of 49 ± 11 years) characterized for dietary, lifestyle habits and anthropometry, were studied for presence and severity of COVID-19 infection, and genotyped for 26 genetic variants related to obesity, lipid profile, inflammation, and biorhythm patterns. A statistically significant association was found concerning a protective effect of APOE rs7412 against SARS-CoV-2 infection (p = 0.039; OR 0.216; CI 0.084, 0.557) after correction for multiple comparisons. This protective effect was also ascribed to the APOÉ2 allele (p = 0.001; OR 0.207; CI 0.0796, 0.538). The genetic variant rs7412 resulting in ApoE2, genetic determinant of lipid and lipoprotein levels, could play a significant role protecting against SARS-CoV-2 infection.
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Apolipoproteínas E/genética , COVID-19 , Adulto , Apolipoproteína E2 , COVID-19/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/genética , Pandemias , SARS-CoV-2RESUMO
Objective: This article describes the methodology and summarizes some preliminary results of the GENYAL study aiming to design and validate a predictive model, considering both environmental and genetic factors, that identifies children who would benefit most from actions aimed at reducing the risk of obesity and its complications. Design: The study is a cluster randomized clinical trial with 5-year follow-up. The initial evaluation was carried out in 2017. The schools were randomly split into intervention (nutritional education) and control schools. Anthropometric measurements, social and health as well as dietary and physical activity data of schoolchildren and their families are annually collected. A total of 26 single nucleotide polymorphisms (SNPs) were assessed. Machine Learning models are being designed to predict obesity phenotypes after the 5-year follow-up. Settings: Six schools in Madrid. Participants: A total of 221 schoolchildren (6-8 years old). Results: Collected results show that the prevalence of excess weight was 19.0, 25.4, and 32.2% (according to World Health Organization, International Obesity Task Force and Orbegozo Foundation criteria, respectively). Associations between the nutritional state of children with mother BMI [ß = 0.21 (0.13-0.3), p (adjusted) <0.001], geographical location of the school [OR = 2.74 (1.24-6.22), p (adjusted) = 0.06], dairy servings per day [OR = 0.48 (0.29-0.75), p (adjusted) = 0.05] and 8 SNPs [rs1260326, rs780094, rs10913469, rs328, rs7647305, rs3101336, rs2568958, rs925946; p (not adjusted) <0.05] were found. Conclusions: These baseline data support the evidence that environmental and genetic factors play a role in the development of childhood obesity. After 5-year follow-up, the GENYAL study pretends to validate the predictive model as a new strategy to fight against obesity. Clinical Trial Registration: This study has been registered in ClinicalTrials.gov with the identifier NCT03419520, https://clinicaltrials.gov/ct2/show/NCT03419520.
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Precision public health supported on online tools is increasingly emerging as a potential strategy to achieve health promotion and disease prevention. Our aim was to assess the relationships of sociodemographic variables, anthropometric data, dietary habits and lifestyle factors with health-related quality of life (HRQoL), cardiometabolic health status and ethnicity in an online recruited adult population (NutrIMDEA Study). NutrIMDEA Study is a web-based cross-sectional survey that included 17,333 adults. Self-reported sociodemographic characteristics, anthropometric data, clinical and family history of cardiometabolic illnesses, dietary habits, lifestyle factors and HRQoL features were collected. Diseased individuals showed significative poorer MedDiet and worse HRQoL than those in the healthy cardiometabolic status group (p < 0.05). In comparison, European/Caucasian individuals reported a significantly better HRQoL, higher MedDiet and HRQoL values compared with those of other ethnicities (p < 0.05). We obtained a total of 16.8% who reported poor/fair, 56.5% good and 26.6% very good/excellent HRQoL. Respondents with very good/excellent HRQoL showed lower BMI, greater adherence to a Mediterranean diet (MedDiet) and higher physical activity. The results suggest the presence of interactions between the mental and physical components of HRQoL with obesity, sedentarism and dietary intake, which were dependent on disease status and ethnicity. Online HRQoL assessment could contribute to wider implementation of precision public health strategies to promote health targeted interventions with policy implications to community health promotion.
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Doenças Cardiovasculares , Qualidade de Vida , Adulto , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Etnicidade , Promoção da Saúde , Nível de Saúde , Humanos , InternetRESUMO
Sport performance is influenced by several factors, including genetic susceptibility. In the past years, specific single nucleotide polymorphisms have been associated to sport performance; however, these effects should be considered in multivariable prediction systems since they are related to a polygenic inheritance. The aim of this study was to design a genetic endurance prediction score (GES) of endurance performance and analyze its association with anthropometric, nutritional and sport efficiency variables in a cross-sectional study within fifteen male cyclists. A statistically significant positive relationship between GES and the VO2 maximum (P = 0.033), VO2 VT1 (P = 0.049) and VO2 VT2 (P < 0.001) was observed. Moreover, additional remarkable associations between genotype and the anthropometric, nutritional and sport performance variables, were achieved. In addition, an interesting link between the habit of consuming caffeinated beverages and the GES was observed. The outcomes of the present study indicate a potential use of this genetic prediction algorithm in the sports' field, which may facilitate the finding of genetically talented athletes, improve their training and food habits, as well as help in the improvement of physical conditions of amateurs.
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Chronobiological aspects controlled by CLOCK genes may influence obesity incidence. Although there are studies that show an association between the expression of these genes and energy intake, waist circumference or abdominal obesity phenotypes, interactions with appetite have been insufficiently investigated in relation to chrononutrition. The objective was to identify interactions between CLOCK genetic variants involved in appetite status. A total of 442 subjects (329 women, 113 men; aged 18 to 65 years) were recruited. Anthropometric, dietary and lifestyle data were collected by trained nutritionists. Participants were classified according to their appetite feelings with a Likert scale. Multiple linear regression models were used to examine associations of the type genotype x appetite status on adiposity-related variables. p values were corrected by the Bonferroni method. A significant influence was found concerning the effects of appetite on waist circumference with respect to rs3749474 CLOCK polymorphism (p < 0.001). An additive model analysis (adjusted by age, gender, exercise and energy intake) showed that risk allele carriers, increased the waist circumference around 14 cm (ß = 14.1, CI = 6.3-22.0) by each increment in the level of appetite. The effects of appetite on waist circumference may be partly modulated by the rs3749474 CLOCK polymorphism.
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Gordura Abdominal/metabolismo , Apetite , Proteínas CLOCK/genética , Ritmo Circadiano/genética , Obesidade Abdominal/genética , Polimorfismo Genético , Circunferência da Cintura , Adolescente , Adulto , Idoso , Alelos , Regulação do Apetite , Fenômenos Cronobiológicos , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/genética , Obesidade/metabolismo , Obesidade Abdominal/etiologia , Obesidade Abdominal/metabolismo , Adulto JovemRESUMO
Exercise performance is influenced by genetics. However, there is a lack of knowledge about the role played by genetic variability in the frequency of physical exercise practice. The objective was to identify genetic variants that modulate the commitment of people to perform physical exercise and to detect those subjects with a lower frequency practice. A total of 451 subjects were genotyped for 64 genetic variants related to inflammation, circadian rhythms, vascular function as well as energy, lipid and carbohydrate metabolism. Physical exercise frequency question and a Minnesota Leisure Time Physical Activity Questionnaire (MLTPAQ) were used to qualitatively and quantitatively measure the average amount of physical exercise. Dietary intake and energy expenditure due to physical activity were also studied. Differences between genotypes were analyzed using linear and logistic models adjusted for Bonferroni. A significant association between GCKR rs780094 and the times the individuals performed physical exercise was observed (p = 0.004). The carriers of the minor allele showed a greater frequency of physical exercise in comparison to the major homozygous genotype carriers (OR: 1.86, 95% CI: 1.36-2.56). The analysis of the GCKR rs780094 variant suggests a possible association with the subjects that present lower frequency of physical exercise. Nevertheless, future studies are needed to confirm these findings.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Exercício Físico , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND & AIMS: Calcium and dairy products have multiple health benefits. The objective of this work was to evaluate the association between calcium/dairy intake, blood pressure, the BDNF-AS rs925946 polymorphism and nutritional status in a group of schoolchildren. METHODS: As part of the GENYAL study to childhood obesity prevention, 221 children belonging to different areas of the Community of Madrid were enrolled. Anthropometric and dietary data were collected, and children were genotyped according to the rs925946 polymorphism. Adjusted logistic and linear models were used to describe the data. RESULTS: A significantly lower consumption of calcium in overweight versus normal weight children was observed (811.0 ± 174.1; 859.0 ± 195.9; 954.0 ± 223.1 mg; for obesity, overweight and normal weight, respectively, p = 0.010). Moreover, an inverse association between blood pressures and calcium intake was detected (ß = -0.006 (-0.011, -3e-4)), p = 0.040. The number of dairy servings/day showed a protective effect against overweight (OR = 0.48 (0.29, 0.75), p = 0.001). Finally, common homozygous children (GG) showed an inverse association between the calcium intake and the BMI (ß = -0.003 (-0.006, -0.001), p = 0.004), which was not observed in children carrying the T allele (ß = -1.3e-4 (-0.0022, 0.0024), p = 0.93). CONCLUSION: Calcium and dairy were strongly associated with the nutritional status and blood pressure. The identification of differential effects of calcium/dairy consumption on the nutritional status according to genetics may contribute to the personalization of future nutritional advice. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.govNCT03419520.
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Fator Neurotrófico Derivado do Encéfalo/genética , Cálcio da Dieta/análise , Laticínios/estatística & dados numéricos , Obesidade Infantil , RNA Antissenso/genética , Antropometria , Criança , Estudos de Coortes , Dieta/estatística & dados numéricos , Feminino , Humanos , Masculino , Obesidade Infantil/epidemiologia , Obesidade Infantil/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
BACKGROUND AND OBJECTIVE: Multiple chemical sensitivity (MCS) is a complex, acquired, chronic syndrome of multifactorial etiology with multiple symptoms. The aim of the study was to assess the nutritional habits, dietary characteristics and physical activity, as well as their determinants, of a population diagnosed with MCS, which may allow for a more precise approach to nutritional improvement. PATIENTS AND METHOD: A descriptive, cross-sectional study in patients diagnosed with MCS. Information was collected using adapted questionnaires. Data included presence of comorbidities, nutritional (use of supplements, types of diet) and food purchasing habits. Dietary intake, food intolerances, and physical activity were also recorded. RESULTS: The study included of 52 patients (48 female) aged 50.9±10.3 years. Diagnosis of MCS was commonly associated to chronic fatigue syndrome (70.1%), fibromyalgia (65.4%), or electrosensitivity (51.9%). The most common comorbidities were irritable bowel, gastroesophageal reflux, and depression/anxiety-depressive disorder. Exclusion diets were followed by 57.7%, 52.1% commonly used supplements (6.4±5.2 per person), and 16.0% took more than 10 daily. A high proportion of volunteers did not take the recommended amounts of dairy products (84.3%), fruit (82.3%), and cereals (64.7%), the foods to which intolerance was greatest. As regards physical activity, active subjects only represented 12.5%. CONCLUSIONS: The data collected support the need to improve food pattern and to perform physical activity according to individual characteristics. Nutritional education and diet personalization could prevent incomplete, monotonous, and unbalanced diets which impair quality of life and physiological status.
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Dieta , Exercício Físico , Sensibilidade Química Múltipla/epidemiologia , Adulto , Idoso , Asma/epidemiologia , Comorbidade , Estudos Transversais , Laticínios , Depressão/epidemiologia , Suplementos Nutricionais , Grão Comestível , Síndrome de Fadiga Crônica/epidemiologia , Síndrome de Fadiga Crônica/etiologia , Comportamento Alimentar , Feminino , Refluxo Gastroesofágico/epidemiologia , Humanos , Hipercolesterolemia/epidemiologia , Hipersensibilidade/epidemiologia , Hipotireoidismo/epidemiologia , Síndrome do Intestino Irritável/epidemiologia , Masculino , Pessoa de Meia-Idade , Sensibilidade Química Múltipla/etiologia , Espanha/epidemiologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND OBJECTIVES: Multiple chemical sensitivity (MCS) is a chronic, multisystem syndrome of unknown etiology. The aim of the present study was to describe the nutritional status and quality of life of patients suffering from MCS, as well as to identify potential polymorphisms associated with this illness. PATIENTS AND METHODS: A cross-sectional, descriptive study was performed on patients with a diagnosis of MCS. Data on anthropometric and body composition variables, hand muscle strength and quality of life were collected. The selection of single nucleotide polymorphisms (SNPs) was based on genes previously associated with MCS and genes involved in inflammatory and oxidative stress pathways. RESULTS: A total of 52 patients (93.2% female), with a mean age of 50.9 (10.3) years were included in the study. Among them, based on their BMI, 48% had an inadequate nutritional status (17% were underweight and 32% were overweight or obese). Thirty percent of patients had a low muscle mass for their age, 84% had muscle strength below the tenth percentile, and 51.8% had a high fat mass percentage. Regarding quality of life, all median scores were lower than those of other illnesses assessed for every subscale assessed. Statistically significant differences between patient cases and controls were found with respect to rs1801133 (MTHFR), rs174546 (FADS1) and rs1801282 (PPARγ) polymorphisms. CONCLUSION: A high percentage of patients had a poor nutritional status, low muscle strength and decreased muscle mass. These facts exacerbate the already-lower quality of life of these patients. Specific genetic polymorphisms associated with the syndrome or its pathogenesis were not identified.
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Genótipo , Sensibilidade Química Múltipla , Estado Nutricional , Sobrepeso/etiologia , Polimorfismo de Nucleotídeo Único , Qualidade de Vida , Magreza/etiologia , Adulto , Composição Corporal , Estudos Transversais , Dessaturase de Ácido Graxo Delta-5 , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade Química Múltipla/complicações , Sensibilidade Química Múltipla/diagnóstico , Sensibilidade Química Múltipla/genética , Sensibilidade Química Múltipla/fisiopatologia , Sobrepeso/diagnóstico , Sobrepeso/epidemiologia , Magreza/diagnóstico , Magreza/epidemiologiaRESUMO
OBJECTIVES: The aim of this study was to assess the effect of a weight loss treatment on obesity- associated variables with respect to the CLOCK and FTO genotypes. METHODS: In all, 179 volunteers (78% female) participated in a 12-week calorie-restriction program; hypocaloric diets of between 5442 and 10048 kJ/d were individually prescribed to all participants. Dietetic, anthropometric, and biochemical data were collected at baseline and at the end of the intervention. When treatment was over, five single nucleotide polymorphisms (SNPs) were sought in CLOCK and FTO in all participants who provided consent. Bonferroni-corrected linear regression models were used to examine the influence of interactions of the type genotype × dietetic change on obesity-associated variables. RESULTS: Variation in the CLOCK and FTO genotypes had no significant influence on the change in obesity-associated variables. The interaction genotype × percentage intake of dietary fat had a significant influence on body mass index (BMI; adjusted P = 0.03). Participants carrying CLOCK rs3749474 (TT + CT) showed a positive association between the change in percentage intake of dietary fat and change in BMI (ß = 0.044; 95% confidence interval [CI], 0.0119-0.0769; P = 0.008), whereas participants homozygous for the wild-type allele (CC) showed a negative, although nonsignificant association (ß = -0.032; 95% CI, -0.0694 to 0.036; P = 0.077). CONCLUSION: The possession of CLOCK rs3749474 may influence the effect of reducing the percentage intake of dietary fat on obesity-associated variables. Participants carrying this SNP might benefit more than others from weight loss treatment involving dietary fat restriction. The treatment of obesity might therefore be customized, depending on the alleles carried.
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Proteínas CLOCK/genética , Restrição Calórica , Gorduras na Dieta/administração & dosagem , Obesidade/genética , Redução de Peso/genética , Adulto , Alelos , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , Glicemia/metabolismo , Índice de Massa Corporal , Proteínas CLOCK/metabolismo , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Carboidratos da Dieta/administração & dosagem , Carboidratos da Dieta/análise , Gorduras na Dieta/análise , Proteínas Alimentares/administração & dosagem , Proteínas Alimentares/análise , Ingestão de Energia , Exercício Físico , Feminino , Interação Gene-Ambiente , Humanos , Resistência à Insulina , Masculino , Avaliação Nutricional , Obesidade/dietoterapia , Polimorfismo de Nucleotídeo Único , Triglicerídeos/sangueRESUMO
Lipid metabolism plays an essential role in carcinogenesis due to the requirements of tumoral cells to sustain increased structural, energetic and biosynthetic precursor demands for cell proliferation. We investigated the association between expression of lipid metabolism-related genes and clinical outcome in intermediate-stage colon cancer patients with the aim of identifying a metabolic profile associated with greater malignancy and increased risk of relapse. Expression profile of 70 lipid metabolism-related genes was determined in 77 patients with stage II colon cancer. Cox regression analyses using c-index methodology was applied to identify a metabolic-related signature associated to prognosis. The metabolic signature was further confirmed in two independent validation sets of 120 patients and additionally, in a group of 264 patients from a public database. The combined analysis of these 4 genes, ABCA1, ACSL1, AGPAT1 and SCD, constitutes a metabolic-signature (ColoLipidGene) able to accurately stratify stage II colon cancer patients with 5-fold higher risk of relapse with strong statistical power in the four independent groups of patients. The identification of a group of 4 genes that predict survival in intermediate-stage colon cancer patients allows delineation of a high-risk group that may benefit from adjuvant therapy, and avoids the toxic and unnecessary chemotherapy in patients classified as low-risk group.
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Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Metabolismo dos Lipídeos , 1-Acilglicerol-3-Fosfato O-Aciltransferase/genética , 1-Acilglicerol-3-Fosfato O-Aciltransferase/metabolismo , Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proliferação de Células , Neoplasias Colorretais/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Recidiva , Análise de Regressão , Estudos Retrospectivos , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: The association of dairy food consumption with the risk for developing cardiovascular disease (CVD) has been investigated in many studies, but results often have been contradictory. The aim of the present study was to determine whether genetic polymorphisms are associated with interindividual variation in the response of CVD risk biomarker values after milk consumption. METHODS: Fourteen single nucleotide polymorphisms (SNPs) in nine genes related to lipid metabolism were examined in 161 volunteers randomly allocated to consume either 500 mL/d of skimmed (S) or semi-skimmed (SS) milk for 1 year in addition to their usual diets. Total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) and low-density lipoprotein/HDL-C ratios were used as biomarkers of CVD risk. Three-way repeated-measures analysis of variance was used to examine the effect of time, treatment (S or SS), and genotype on these biomarkers. RESULTS: A TT genotype for the proliferator-activated receptor alpha polymorphism (PPARA rs135549 SNP) was significantly associated with a reduction in the TC/HDL and LDL/HDL ratios after 12 mo of S milk intake (mean reduction -0.29, 95% confidence interval [CI], -0.63 to 0.05; P = 0.0015 and -0.31, 95% CI, -0.58 to -0.03; P = 0.0005, respectively). However, no differences were observed after consuming either S or SS milk in the C allele carriers. CONCLUSIONS: Saturated fatty acid consumption has long been linked to an increased risk for CVD; indeed, the consumption of saturated fat-free products is recommended as a means of reducing this risk. However, the present results suggest that many individuals might not benefit from such general recommendations. Genetic analysis of PPARA rs135549 might help identify those individuals who are more likely to benefit from reducing the saturated fatty acid content of their diet.