RESUMO
MicroRNAs (miRNAs), particularly miR-16 and miR-21, play a crucial role in multiple myeloma (MM) pathogenesis by regulating gene expression. This study evaluated the prognostic significance of circulating miR-16 and miR-21 expression levels in 48 patients with MM at diagnosis treated with lenalidomide-dexamethasone (LD) compared with 15 healthy individuals (HI). All patients were treated with LD, 13 at first line and 35 at relapse, of whom 21 were tested twice at diagnosis and before LD initiation. The results revealed significantly lower levels of miR-16 and miR-21 in patients than in HIs, both at diagnosis and relapse, with decreased miR-16 levels at diagnosis, indicating improved overall survival (OS) (p value 0.024). Furthermore, miR-16 and miR-21 levels were associated with disease markers, while both correlated with the depth of response and mir-16 with sustained response to LD treatment. Ratios of both miR-16 and miR-21 expression levels (prior to LD treatment/diagnosis) below two predicted a shorter time to response (p = 0.027) and a longer time to next treatment (p = 0.042), respectively. These findings suggested a prognostic value for serum miR-16 and miR-21 levels in MM, as their expression levels correlated with disease variables and treatment outcomes.
Assuntos
Lenalidomida , MicroRNAs , Mieloma Múltiplo , Talidomida , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/sangue , Mieloma Múltiplo/mortalidade , MicroRNAs/sangue , MicroRNAs/genética , Lenalidomida/uso terapêutico , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Prognóstico , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Dexametasona/uso terapêutico , Idoso de 80 Anos ou mais , Adulto , Regulação Neoplásica da Expressão Gênica , MicroRNA Circulante/sangue , Resultado do TratamentoRESUMO
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.
Assuntos
Biomarcadores , Dieta Mediterrânea , Exercício Físico , Estilo de Vida , Hepatopatia Gordurosa não Alcoólica , Humanos , Masculino , Grécia/epidemiologia , Feminino , Fatores de Risco , Estudos de Casos e Controles , Pessoa de Meia-Idade , Biomarcadores/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Adulto , Índice de Massa Corporal , Metaboloma , Fumar , Idoso , Metabolômica/métodos , Espectroscopia de Ressonância MagnéticaRESUMO
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.
Assuntos
Doenças Cardiovasculares , Fator A de Crescimento do Endotélio Vascular , Humanos , Adolescente , Fator A de Crescimento do Endotélio Vascular/genética , Estudos Transversais , Dieta , Fatores de Risco , Doenças Cardiovasculares/genéticaRESUMO
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.
Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Diabetes Mellitus Tipo 2/complicações , Fibrose , Humanos , Inflamação/complicações , Fígado/patologia , Imageamento por Ressonância Magnética/métodos , Hepatopatia Gordurosa não Alcoólica/epidemiologiaRESUMO
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.
Assuntos
Comportamento Alimentar , Indicadores Básicos de Saúde , Estilo de Vida , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Adulto , Antropometria , Glicemia/análise , Composição Corporal , Índice de Massa Corporal , Restrição Calórica/métodos , Inquéritos sobre Dietas , Feminino , Grécia , Humanos , Gordura Intra-Abdominal/fisiopatologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Nutrientes/administração & dosagem , Fenômenos Fisiológicos da Nutrição/genética , Estado Nutricional , Obesidade/genética , Obesidade/terapia , Sobrepeso/genética , Sobrepeso/terapia , Análise de Componente Principal , Estudos Prospectivos , Programas de Redução de Peso/métodosRESUMO
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease with no therapeutic consensus. Oxidation and inflammation are hallmarks in the progression of this complex disease, which also involves interactions between the genetic background and the environment. Mastiha is a natural nutritional supplement known to possess antioxidant and anti-inflammatory properties. This study investigated how a 6-month Mastiha supplementation (2.1 g/day) could impact the antioxidant and inflammatory status of patients with NAFLD, and whether genetic variants significantly mediate these effects. We recruited 98 patients with obesity (BMI ≥ 30 kg/m2) and NAFLD and randomly allocated them to either the Mastiha or the placebo group for 6 months. The anti-oxidative and inflammatory status was assessed at baseline and post-treatment. Genome-wide genetic data was also obtained from all participants, to investigate gene-by-Mastiha interactions. NAFLD patients with severe obesity (BMI > 35kg/m2) taking the Mastiha had significantly higher total antioxidant status (TAS) compared to the corresponding placebo group (P value=0.008). We did not observe any other significant change in the investigated biomarkers as a result of Mastiha supplementation alone. We identified several novel gene-by-Mastiha interaction associations with levels of cytokines and antioxidant biomarkers. Some of the identified genetic loci are implicated in the pathological pathways of NAFLD, including the lanosterol synthase gene (LSS) associated with glutathione peroxidase activity (Gpx) levels, the mitochondrial pyruvate carrier-1 gene (MPC1) and the sphingolipid transporter-1 gene (SPNS1) associated with hemoglobin levels, the transforming growth factor-beta-induced gene (TGFBI) and the micro-RNA 129-1 (MIR129-1) associated with IL-6 and the granzyme B gene (GZMB) associated with IL-10 levels. Within the MAST4HEALTH randomized clinical trial (NCT03135873, www.clinicaltrials.gov) Mastiha supplementation improved the TAS levels among NAFLD patients with severe obesity. We identified several novel genome-wide significant nutrigenetic interactions, influencing the antioxidant and inflammatory status in NAFLD. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03135873.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Suplementos Nutricionais , Resina Mástique/química , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Nutrigenômica , Adulto , Idoso , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Biomarcadores , Gerenciamento Clínico , Suscetibilidade a Doenças , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/etiologia , Nutrigenômica/métodos , Estresse Oxidativo/efeitos dos fármacos , Adulto JovemRESUMO
CONTEXT: Geographic distribution of ATP7B mutations in different populations. OBJECTIVE: To summarise common mutations in the ATP7B gene and graphically illustrate their prevalence in different populations. METHODS: A literature search was done using PubMed and the Wilson Disease Mutation Database (http://www.wilsondisease.med.ualberta.ca/database). RESULTS: p.His1069Gln is the most prevalent mutation seen in Europe. In the Mediterranean countries, the array of prevalent mutations is different from the rest of Europe. In Far East Asian countries, the mutation p.Arg778Leu is the most common. In India, no single mutation seems to be dominant, owing to the vast ethnic diversity of the country. The p.Cys271* mutation is dominant in the east, west and south, but not reported in the north. In the Middle East, data from Saudi Arabia shows the p.Gln1399Arg mutation as the most prevalent. In the US, the p.His1069Gln is dominant, whereas in Brazil the mutation c.3402delC dominates. CONCLUSION: Clinical features in WD patients can be misleading and often absent. Genetic testing is used to confirm the diagnosis. However, owing to the large gene size and vast diversity in the mutations, genetic testing can be time-consuming and tedious. This study reviews ATP7B mutations seen in different populations and can help develop time-saving methods and expediate the process of genetic analysis of WD.
Assuntos
Adenosina Trifosfatases/genética , Proteínas de Transporte de Cátions/genética , Degeneração Hepatolenticular/epidemiologia , Degeneração Hepatolenticular/genética , Mutação , Cobre , ATPases Transportadoras de Cobre , Dieta , Europa (Continente) , Geografia , Humanos , PrevalênciaRESUMO
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.
Assuntos
Doença da Artéria Coronariana/prevenção & controle , Azeite de Oliva/administração & dosagem , Adulto , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dieta Saudável , Dieta Mediterrânea , Exercício Físico , Feminino , Grécia , Humanos , Estilo de Vida , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Fatores de Risco , Fatores Socioeconômicos , Triglicerídeos/sangueRESUMO
Recent genome wide association studies (GWAS) have identified a locus on chromosome 11p15.5, closely associated with serine/threonine kinase 33 (STK33), to be associated with body mass. STK33, a relatively understudied protein, has been linked to KRAS mutation-driven cancers and explored as a potential antineoplastic drug target. The strongest association with body mass observed at this loci in GWAS was rs4929949, a single nucleotide polymorphism located within intron 1 of the gene encoding STK33. The functional implications of rs4929949 or related variants have not been explored as of yet. We have genotyped rs4929949 in two cohorts, an obesity case-control cohort of 991 Swedish children, and a cross-sectional cohort of 2308 Greek school children. We found that the minor allele of rs4929949 was associated with obesity in the cohort of Swedish children and adolescents (ORâ=â1.199 (95%CI: 1.002-1.434), pâ=â0.047), and with body mass in the cross-sectional cohort of Greek children (ßâ=â0.08147 (95% CI: 0.1345-0.1618), pâ=â0.021). We observe the effects of rs4929949 on body mass to be detectable already at adolescence. Subsequent analysis did not detect any association of rs4929949 to phenotypic measurements describing body adiposity or to metabolic factors such as insulin levels, triglycerides and insulin resistance (HOMA).
Assuntos
Índice de Massa Corporal , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Proteínas Serina-Treonina Quinases/genética , Alelos , Criança , Estudos de Coortes , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Grécia , Haplótipos , Humanos , Masculino , Suécia , Regiões não TraduzidasRESUMO
OBJECTIVE: To investigate whether associations of common genetic variants recently identified for fasting glucose or insulin levels in nondiabetic adults are detectable in healthy children and adolescents. RESEARCH DESIGN AND METHODS: A total of 16 single nucleotide polymorphisms (SNPs) associated with fasting glucose were genotyped in six studies of children and adolescents of European origin, including over 6,000 boys and girls aged 9-16 years. We performed meta-analyses to test associations of individual SNPs and a weighted risk score of the 16 loci with fasting glucose. RESULTS: Nine loci were associated with glucose levels in healthy children and adolescents, with four of these associations reported in previous studies and five reported here for the first time (GLIS3, PROX1, SLC2A2, ADCY5, and CRY2). Effect sizes were similar to those in adults, suggesting age-independent effects of these fasting glucose loci. Children and adolescents carrying glucose-raising alleles of G6PC2, MTNR1B, GCK, and GLIS3 also showed reduced ß-cell function, as indicated by homeostasis model assessment of ß-cell function. Analysis using a weighted risk score showed an increase [ß (95% CI)] in fasting glucose level of 0.026 mmol/L (0.021-0.031) for each unit increase in the score. CONCLUSIONS: Novel fasting glucose loci identified in genome-wide association studies of adults are associated with altered fasting glucose levels in healthy children and adolescents with effect sizes comparable to adults. In nondiabetic adults, fasting glucose changes little over time, and our results suggest that age-independent effects of fasting glucose loci contribute to long-term interindividual differences in glucose levels from childhood onwards.
Assuntos
Glicemia/genética , Jejum/sangue , Loci Gênicos/genética , Adenilil Ciclases/genética , Adolescente , Criança , Criptocromos/genética , Proteínas de Ligação a DNA , Feminino , Estudo de Associação Genômica Ampla , Quinases do Centro Germinativo , Transportador de Glucose Tipo 2/genética , Glucose-6-Fosfatase/genética , Proteínas de Homeodomínio/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Repressoras , Transativadores , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
OBJECTIVE: To evaluate potential associations between diet- and physical activity-related lifestyle patterns and obesity indices in a cohort of children. STUDY DESIGN: Dietary and physical activity information and anthropometric indices were collected from 1138 children (53% girls; age, 11.2 ± 0.7 years). Dietary intake was evaluated with two 24-hour recalls, which were analyzed for nutrient and food intake, eating frequency, and meal quality. Principal component analysis was used to extract salient lifestyle patterns. RESULTS: Five lifestyle behavioral patterns were identified. The "dinner, cooked meals and vegetables pattern," a multidimensional lifestyle pattern including the consumption of vegetables, cooked meals, and eating dinner, was negatively associated with all obesity indices, even after adjustment for potential confounders and exclusion of low energy reporters. A "high fiber pattern," representing high consumption of whole-grain cereals, legumes, and low intake of sugar-sweetened beverages was negatively correlated with obesity indices; when the analysis included only acceptable energy reporters, these associations became non-significant, except for triceps skinfolds. CONCLUSIONS: Our findings are supportive of the synergistic or conditional effects of distinct lifestyle-related behaviors on obesity. Although these results are hypothesis-generating and need replication, they suggest potential preventive approaches, interventional approaches, or both to combat childhood obesity.
Assuntos
Culinária , Dieta , Comportamento Alimentar , Estilo de Vida , Atividade Motora , Sobrepeso/epidemiologia , Verduras , Criança , Estudos Transversais , Feminino , Humanos , MasculinoRESUMO
Polymorphisms in the endothelial nitric oxide synthase ( eNOS ) gene (- 786T > C and 894G > T ) enhance endothelial dysfunction and have been studied in relation to coronary artery disease (CAD). In the present study, we examined the association of the above polymorphisms with CAD, as well as with myocardial infarction (MI), hypertension, diabetes and smoking in CAD patients. Study subjects consisted of 154 consecutive coronary artery bypass graft (CABG) patients and 155 non-CAD controls. eNOS - 786T > C and 894G > T polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism. The estimated frequencies of the - 786C and 894T alleles did not differ between the two groups ( p = 0.46 and p = 0.84, respectively). The prevalence of eNOS polymorphisms was not associated with MI, hypertension or diabetes in CABG patients; however, we found that the 894TT genotype and 894T allele were significantly more frequent in current/past smoker CABG patients (16.7 per cent and 39.6 per cent, respectively) compared with never smoker CABG patients (6.1 per cent and 24.4 per cent, respectively) ( p = 0.01 and p < 0.01, respectively). We found no association of eNOS - 786C and 894T variant alleles with CAD; however, within CABG patients, a gene-environment interaction was found between the eNOS 894T allele and smoking.
Assuntos
Ponte de Artéria Coronária , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fumar/genéticaRESUMO
BACKGROUND: Adipose tissue secrets several adipokines that have been proposed to be enrolled in many inflammatory pathways. Our aim was to investigate the adipokine expression in adipose tissue and peripheral blood mononuclear cells (PBMCs) in children. MATERIALS AND METHODS: Thirty-one (17 males and 14 females) healthy children aged 10.9 +/- 1.8 years with a body mass index (BMI) of 19.3 +/- 3.5 kg m(-2) were enrolled. Adipokines (TNF-alpha, IL-6 and leptin) gene expression was quantified by real-time quantitative PCR in adipose tissue and PBMCs from the same children. Their serum levels were also measured. RESULTS: BMI was positively correlated with leptin gene expression in adipose tissue and with leptin serum levels (beta = 0.476, P = 0.006 and beta = 0.576, P = 0.003 respectively). Leptin's serum levels were positively correlated with leptin gene expression in adipose tissue (beta = 0.462, P = 0.02). Adipose tissue gene expression of leptin and TNF-alpha and serum leptin and TNF-alpha serum levels were positively correlated (beta = 0.752, P < 0.001, beta = 0.311 and P = 0.015 respectively). In PBMCs, a positive correlation between TNF-alpha and IL-6 expression was found (beta = 0.526, P = 0.042). CONCLUSION: We demonstrated powerful correlations of adipokines gene expression in adipose tissue and PBMCs in children, underlying that these molecules share common pathways related to childhood obesity.
Assuntos
Adipocinas/sangue , Tecido Adiposo/química , Células Sanguíneas/química , Inflamação , Interleucina-6/sangue , Fator de Necrose Tumoral alfa/sangue , Adipocinas/análise , Adolescente , Índice de Massa Corporal , Criança , Feminino , Expressão Gênica , Humanos , Interleucina-6/análise , Masculino , Obesidade , Fator de Necrose Tumoral alfa/análiseRESUMO
INTRODUCTION: Candidates for coronary artery bypass grafting (CABG) represent a group of patients with well documented, severe coronary artery disease (CAD). Genetic polymorphisms of renin-angiotensin-aldosterone system (RAAS) components have been associated with CAD. We examined the association of polymorphisms of angiotensin-converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II type 1 receptor (AT(1) receptor) with severe CAD in CABG patients. MATERIALS AND METHODS: One hundred and fifty-four CABG patients and 155 non-CAD controls were included in the study. Established PCR methods were used for genotyping of AGT M235T, AGT T174M, AT(1) receptor A1166C, and ACE I/D polymorphisms. Cumulative effect of analysed polymorphisms was assessed by calculation of each individual's RAAS gene score (addition of 0.5 points for each variant allele and then calculating the sum for all four polymorphisms). RESULTS: No association between AGT M235T, AGT T174M, ACE I/D and AT(1) receptor A1166C polymorphisms and CAD was observed. Within CABG patients, the frequency of homozygous AGT 235TT genotype was higher in hypertensive compared to normotensive CABG patients (21.7% vs. 6.3%, p=0.03). RAAS gene score did not differ between CABG patients and non-CAD controls. CONCLUSIONS: There is no association of the analysed RAAS polymorphisms with severe CAD in CABG patients. However, within these patients, an association was found between AGT 235TT genotype and hypertension.
Assuntos
Ponte de Artéria Coronária , Polimorfismo Genético , Sistema Renina-Angiotensina/genética , Idoso , Idoso de 80 Anos ou mais , Angiotensinogênio/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Hipertensão/genética , Masculino , Pessoa de Meia-IdadeRESUMO
Although zinc plays an important role in health status of the elderly, their dietary habits in relation to zinc intake are not well documented. The main objective of the current study was the assessment of dietary zinc intake in European old populations and the investigation of its impact on plasma zinc and inflammatory cytokines concentrations, in relation to genetic markers. Within the ZINCAGE study, 819 healthy old Europeans (>or=60 years old) were recruited. Plasma zinc, interleukin-6 (IL-6) and interleukin-8 (IL-8) were measured. Genotype data were obtained for the -174G/C polymorphism in the IL-6 gene. Dietary data were collected with a food frequency questionnaire and were used to calculate a zinc diet score. Zinc score was validated using additional dietary data (24-h recalls), in a subsample of 105 subjects. Zinc score was different among most of the European centres (P<.001), while an age-dependent decline was documented (P=4.4x10(-12)). Plasma zinc concentrations were significantly correlated with the zinc score (standardized beta=0.144, P=8.8x10(-5)). The minor allele frequency for the -174G/C polymorphism was f(C) 0.31. There was a significant interaction of zinc diet score and GG (-174G/C) genotype on higher plasma IL-6 levels (beta+/-S.E.=0.014+/-0.0, P=.008). The main finding of our study was the detection of gene-nutrient and biochemical-nutrient interactions in a multiethnic cohort based on a common dietary assessment tool.
Assuntos
Dieta , Ciências da Nutrição , Oligoelementos/administração & dosagem , Zinco/deficiência , Zinco/uso terapêutico , Idoso , Envelhecimento , Estudos de Coortes , Suplementos Nutricionais , Etnicidade , Europa (Continente) , Feminino , Humanos , Inflamação , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Masculino , Polimorfismo Genético , Zinco/administração & dosagemRESUMO
BACKGROUND: Rs619203 (Cys2229Ser) and rs529038 (Asp2213Asn) polymorphisms in the ROS1 gene have been studied in relation to myocardial infarction (MI) yielding inconsistent results. We investigated the role of ROS1 rs529038 polymorphism in coronary artery disease (CAD) in Greeks using a case-control study. METHODS: Genotyping for rs529038 polymorphism was performed using a multiplex PCR technique in patients with CAD (n=294) and controls (n=311). Logistic regression analysis was used to calculate crude and adjusted odds ratios (ORs). RESULTS: Logistic regression analysis did not show any statistically significant effect of ROS1 polymorphism in the occurrence of CAD (AG vs. AA, OR: 1.08, p=0.635; GG vs. AA, OR: 0.62, p=0.220). Adjustment for confounding factors gave similar results, irrespective of the type of disease (i.e., stable coronary artery disease vs. acute coronary syndrome). CONCLUSIONS: Our findings do not support the hypothesis that ROS1 rs529038 polymorphism is an important contributing factor in the etiology of CAD in the Greek population.
Assuntos
Asparagina/genética , Ácido Aspártico/genética , Infarto do Miocárdio/genética , Polimorfismo Genético , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Idoso , Estudos de Casos e Controles , Feminino , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Tirosina Quinases/química , Proteínas Proto-Oncogênicas/químicaRESUMO
OBJECTIVE: Adipose tissue contributes in energy, lipid homeostasis and inflammation, through the adipokines it releases. Our aim was to study the associations between adipose tissue (AT) fatty acid content, adipokines' expression in AT and PBMCs and BMI in children. METHODS: Thirty-one (17 male) healthy children aged 10.9+/-1.8years and of BMI 19.3+/-3.5kg/m(2) were enrolled. Adipokines (TNF-alpha, IL-6, leptin and visfatin) expression was quantified by real-time quantitative PCR in AT and PBMCs. Serum levels were measured by ELISA and fatty acids (FA) from AT by gas chromatography. RESULTS: BMI was correlated with monounsaturated fatty acids (MUFAs) (beta=0.339, p=0.043), arachidonic (AA) (beta=0.576, p< or =0.001) and eicosapentaenoic acids (EPA) (beta=0.404, p=0.004) and negatively with stearic acid (beta=-0.577, p< or =0.001). TNF-alpha and visfatin expression from PBMCs were positively correlated with MUFAs (beta=0.271, p=0.027 and beta=0.214, p=0.020, respectively), n-9 fatty acids (beta=0.313, p=0.010 and beta=0.269 and p=0.024, respectively) and with docosahexaenoic acid (DHA) (beta=0.429, p=0.004 and beta=0.484, p< or =0.001, respectively), while negatively with the ratio n-6/n-3 (beta=-0.490, p=0.007 and beta=-0.374, p=0.044). CONCLUSIONS: A series of FA molecules were correlated with children's BMI and with TNF-alpha and visfatin expression from PBMCs indicating that AT fatty acid content, might have a role, as a potential regulator of PBMCs inflammatory gene expression.
Assuntos
Adipocinas/análise , Tecido Adiposo/química , Índice de Massa Corporal , Ácidos Graxos/análise , Leucócitos Mononucleares/química , Adipocinas/sangue , Células Sanguíneas , Composição Corporal , Criança , Feminino , Humanos , Inflamação , Interleucina-6/análise , Interleucina-6/sangue , Leptina/análise , Leptina/sangue , Masculino , Nicotinamida Fosforribosiltransferase/análise , Nicotinamida Fosforribosiltransferase/sangue , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/sangueRESUMO
Mutations in the SLC3A1 and SLC7A9 genes cause cystinuria (OMIM 220100), an autosomal recessive disorder of amino acid transport and reabsorption in the proximal renal tubule and in the epithelial cells of the gastrointestinal tract. In an attempt to characterize the molecular defect in the SLC3A1 and SLC7A9 genes, we analyzed a cohort of 85 unrelated subjects clinically diagnosed as affected by cystinuria on the basis of stone formation, prevalently of Italian and Greek origin. Analysis of all coding region and exon-intron junctions of the SLC3A1 and SLC7A9 genes by using direct sequencing method allowed us to identify 62 different mutations in 83 out of 85 patients accounting for 90.5% of all affected chromosomes. Twenty-four out of 62 are novel mutations, 9 in SLC3A1 and 15 in SLC7A9. In conclusion, this report expands the spectrum of SLC3A1 and SLC7A9 mutations and confirms the heterogeneity of this disorder.
Assuntos
Sistemas de Transporte de Aminoácidos Básicos/genética , Sistemas de Transporte de Aminoácidos Neutros/genética , Cistinúria/genética , Análise Mutacional de DNA , Mutação , Estudos de Coortes , HumanosRESUMO
BACKGROUND: Aging is associated with low-grade elevation of circulating inflammatory markers, leading to increased risk of morbidity and mortality. The Mediterranean diet has been suggested as a determinant of longevity. In the current study, we investigated the impact of the Mediterranean diet on inflammatory status in old subjects. METHODS: Within the ZINCAGE study, 957 healthy old subjects (>or=60 years old) from five European countries were recruited. Plasma interleukin (IL)-6, IL-8, monocyte chemoattractant protein, tumor necrosis factor-alpha, high-density lipoprotein cholesterol (HDL-C) and erythrocyte sedimentation rate (ESR) were measured. Dietary data were collected applying a food frequency questionnaire and were used to estimate adherence to the Mediterranean diet. RESULTS: The Italians presented the greatest adherence to the Mediterranean diet, while the Polish the poorest. In females, higher diet score was significantly associated with lower body mass index and ESR and higher HDL-C levels (beta=-0.127, p=0.003; beta=-0.144, p=0.001; beta=0.144, p=0.029, respectively). In males, diet score was negatively associated with IL-8 levels (beta=-0.101, p=0.044). The Mediterranean diet was associated with reduced IL-8 concentrations in Greeks (beta=-0.213, p=0.007). CONCLUSIONS: There were significant effects of the components of the Mediterranean diet on inflammation markers. The Mediterranean diet score is useful in assessing nutritional influence on immune status.