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1.
Nat Genet ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578528

RESUMO

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.

2.
Nat Genet ; 51(6): 957-972, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31152163

RESUMO

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.


Assuntos
Estudos de Associação Genética/métodos , Predisposição Genética para Doença , Locos de Características Quantitativas , Característica Quantitativa Herdável , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/fisiopatologia , Mapeamento Cromossômico , Grupo com Ancestrais do Continente Europeu , Estudo de Associação Genômica Ampla , Taxa de Filtração Glomerular , Humanos , Padrões de Herança , Testes de Função Renal , Fenótipo , Polimorfismo de Nucleotídeo Único , Insuficiência Renal Crônica/urina , Uromodulina/urina
3.
Hum Genet ; 138(7): 739-748, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31154530

RESUMO

Metabolic syndrome is a complex human disorder characterized by a cluster of conditions (increased blood pressure, hyperglycemia, excessive body fat around the waist, and abnormal cholesterol or triglyceride levels). Any of these conditions increases the risk of serious disorders such as diabetes or cardiovascular disease. Currently, the degree of genetic regulation of this syndrome is under debate and partially unknown. The principal aim of this study was to estimate the genetic component and the common environmental effects in different populations using full pedigree and genomic information. We used three large populations (Gubbio, ARIC, and Ogliastra cohorts) to estimate the heritability of metabolic syndrome. Due to both pedigree and genotyped data, different approaches were applied to summarize relatedness conditions. Linear mixed models (LLM) using average information restricted maximum likelihood (AIREML) algorithm were applied to partition the variances and estimate heritability (h2) and common sib-household effect (c2). Globally, results obtained from pedigree information showed a significant heritability (h2: 0.286 and 0.271 in Gubbio and Ogliastra, respectively), whereas a lower, but still significant heritability was found using SNPs data ([Formula: see text]: 0.167 and 0.254 in ARIC and Ogliastra). The remaining heritability between h2 and [Formula: see text] ranged between 0.031 and 0.237. Finally, the common environmental c2 in Gubbio and Ogliastra were also significant accounting for about 11% of the phenotypic variance. Availability of different kinds of populations and data helped us to better understand what happened when heritability of metabolic syndrome is estimated and account for different possible confounding. Furthermore, the opportunity of comparing different results provided more precise and less biased estimation of heritability.


Assuntos
Predisposição Genética para Doença , Genética Populacional/métodos , Genoma Humano , Estudo de Associação Genômica Ampla , Genômica/métodos , Síndrome Metabólica/genética , Polimorfismo de Nucleotídeo Único , Estudos de Coortes , Feminino , Genótipo , Humanos , Masculino , Modelos Genéticos , Linhagem
4.
J Am Coll Cardiol ; 73(24): 3118-3131, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31221261

RESUMO

BACKGROUND: Subclinical changes on the electrocardiogram are risk factors for cardiovascular mortality. Recognition and knowledge of electrolyte associations in cardiac electrophysiology are based on only in vitro models and observations in patients with severe medical conditions. OBJECTIVES: This study sought to investigate associations between serum electrolyte concentrations and changes in cardiac electrophysiology in the general population. METHODS: Summary results collected from 153,014 individuals (54.4% women; mean age 55.1 ± 12.1 years) from 33 studies (of 5 ancestries) were meta-analyzed. Linear regression analyses examining associations between electrolyte concentrations (mmol/l of calcium, potassium, sodium, and magnesium), and electrocardiographic intervals (RR, QT, QRS, JT, and PR intervals) were performed. The study adjusted for potential confounders and also stratified by ancestry, sex, and use of antihypertensive drugs. RESULTS: Lower calcium was associated with longer QT intervals (-11.5 ms; 99.75% confidence interval [CI]: -13.7 to -9.3) and JT duration, with sex-specific effects. In contrast, higher magnesium was associated with longer QT intervals (7.2 ms; 99.75% CI: 1.3 to 13.1) and JT. Lower potassium was associated with longer QT intervals (-2.8 ms; 99.75% CI: -3.5 to -2.0), JT, QRS, and PR durations, but all potassium associations were driven by use of antihypertensive drugs. No physiologically relevant associations were observed for sodium or RR intervals. CONCLUSIONS: The study identified physiologically relevant associations between electrolytes and electrocardiographic intervals in a large-scale analysis combining cohorts from different settings. The results provide insights for further cardiac electrophysiology research and could potentially influence clinical practice, especially the association between calcium and QT duration, by which calcium levels at the bottom 2% of the population distribution led to clinically relevant QT prolongation by >5 ms.

5.
Clin Nutr ESPEN ; 29: 160-164, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30661682

RESUMO

BACKGROUND: In subjects with anorexia nervosa (AN) physical exercise may cause or even prevent weight loss, body composition alterations and adaptive thermogenesis. To investigate the influence of behavioral patterns on body composition and energy expenditure in women with AN, we conducted a retrospective analysis in 62 patients with AN referring to our outpatients' clinic. MATERIALS AND METHODS: We assessed anthropometric measurement of weight, height, and BMI; body composition was assessed by bioelectrical impedance analysis; resting energy expenditure was measured through indirect calorimetry. Patients' characteristics were assessed at the time of first evaluation. RESULTS: The subjects were both restricting type (ANR, n = 39) and binge-eating/purging type (ANBP, n = 23) according to DSM-5. We observed a lower reactance (58.63 (11.9) vs. 66.5 (15.5) Ohm, p < 0.05) and higher total body water in ANR subjects. No differences were found in phase angle, fat mass or fat-free mass, nor in REE measures. Within ANR subgroup, we identified two behavioral patterns, with or without physical hyperactivity. Compared to dieting and fasting subjects, hyperactive subjects showed higher phase angle [5.6 (0.7) vs. 4.8 (0.8), p < 0.05], lower fat-free mass [82.5 (6.8) vs. 89.9 (7.5)%, p < 0.05], greater proportion of fat mass [17.5 (6.8) vs. 10.1 (7.5)%, p < 0.05] and body cell mass [46.6 (5.1) vs. 42.5 (5.5)%, p < 0.05]. Finally, hyperactive subjects had greater BMI than dieting or fasting subjects [18.2 (1.7) vs. 15.8 (1.7), p < 0.005]. CONCLUSION: With limitations due to the small sample size, hyperactive subjects show body composition and energy metabolism features that seem protective in terms of prognosis.

6.
Eat Weight Disord ; 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30554325

RESUMO

PURPOSE: Oxidized LDL cholesterol (oxLDL) has been considered as a sensor of oxidative stress (OS) in childhood obesity. We integrated and related our oxLDL existing results previously assessed in overweight/obese children to lifestyle variables to investigate OS-related lifestyle variables. METHODS: 178 Caucasian children/adolescents have been evaluated and according to BMI percentiles have been classified as normal weight (BMI < 75th); overweight (BMI 75-97th) and obese (BMI > 97th). Serum oxLDL levels have been measured. The dietary habits and physical activity have been also assessed. RESULTS: No differences between normal weight and overweight/obese children were detected according to the total score of dietary habits section. Normal weight subjects reported a higher total physical activity score (p = 0.001) compared to overweight/ obese children. No correlation between oxLDL and total dietary habits and physical activity scores was noted. Increased oxLDL in subjects drinking < 1 L/day of water (p = 0.022) and in daily consumers of chocolate drinks at breakfast (p = 0.029) was observed, while a decreased oxLDL was reported in subjects consuming a breakfast based mainly on fruits (p = 0.004). Moreover, "high-fat diet" and "always eating a dessert at the end of the meal" were correlated with increased oxLDL with a trend towards significance. As regards physical activity, no correlations were observed. CONCLUSIONS: Diet and physical activity may not have an immediate impact on OS response in children with or without obesity. Unhealthy lifestyle, including increased fat, simple sugar intake, poor water intake, emerged as external exposome predictors of OS, that may be monitored to improve health status. LEVEL OF EVIDENCE: Level III, case-control analytic studies.

7.
Children (Basel) ; 5(9)2018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-30158481

RESUMO

This paper presents a retrospective cohort study of weight loss medications in young adults aged 21 to 30 following Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) between November 2000 and June 2014. Data were collected from patients who used topiramate, phentermine, and/or metformin postoperatively. Percentage of patients achieving ≥5%, ≥10%, or ≥15% weight loss on medications was determined and percent weight change on each medication was compared to percent weight change of the rest of the cohort. Our results showed that 54.1% of study patients lost ≥5% of their postsurgical weight; 34.3% and 22.9% lost ≥10% and ≥15%, respectively. RYGB had higher median percent weight loss (-8.1%) than SG (-3.3%) (p = 0.0515). No difference was found in median percent weight loss with medications started at weight plateau (-6.0%) versus after weight regain (-5.4%) (p = 0.5304). Patients taking medications at weight loss plateau lost 41.2% of total body weight from before surgery versus 27.1% after weight regain (p = 0.076). Median percent weight change on metformin was -2.9% compared to the rest of the cohort at -7.7% (p = 0.0241). No difference from the rest of the cohort was found for phentermine (p = 0.2018) or topiramate (p = 0.3187). Topiramate, phentermine, and metformin are promising weight loss medications for 21 to 30 year olds. RYGB patients achieve more weight loss on medications but both RYGB and SG benefit. Median total body weight loss from pre-surgical weight may be higher in patients that start medication at postsurgical nadir weight. Participants on metformin lost significantly smaller percentages of weight on medications, which could be the result of underlying medical conditions.

8.
Nutr Diet ; 2018 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-30079594

RESUMO

AIM: The first-line therapy for polycystic ovary syndrome (PCOS) is weight loss focussing on diet and regular exercise; measurement of diet and energy intake (EI) is important to determine associations between nutrients and health in women with PCOS. The EI underreporting (UR) is a condition characterised by reports of habitual EI that is implausibly low, compared with estimated requirements. This case-control study aims to evaluate UR in women with PCOS. METHODS: Thirty-six women with PCOS were enrolled according to the Rotterdam criteria; 37 healthy women were enrolled as controls. INCLUSION CRITERIA: age range 18-45 and body mass index ≥18.5 kg/m2 in subjects without eating disorders and/or diabetes mellitus. Nutritional assessment included: anthropometry, basal metabolic rate (BMR), weight history and physical activity assessment. Subjects completed a non-consecutive three-day dietary diary to identify energy and macronutrient intake. UR was calculated (Goldberg Index: EI/BMR). RESULTS: Although women with PCOS reported a significantly higher mean BMR than controls (P < 0.0001), their EI was lower (P < 0.001), suggesting an UR in 47.2% of women with PCOS versus 2.7% of controls (P < 0.0001). The EI from simple sugars was lower in women with PCOS than controls (P < 0.01). The protein intake was increased in controls than women with PCOS (P < 0.0001). Weight cycling was more frequent in women with PCOS (P < 0.001). Logistic regression analysis identified UR associated with PCOS (P = 0.001). CONCLUSIONS: Women with PCOS underreport foods rich in simple sugars rather than underreport their total dietary intake. These results may have implications for the interpretation of diet and health correlations in this patient population.

9.
Eur J Hum Genet ; 26(8): 1167-1179, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29725052

RESUMO

Age-related hearing loss (ARHL) is the most common sensory disorder in the elderly. Although not directly life threatening, it contributes to loss of autonomy and is associated with anxiety, depression and cognitive decline. To search for genetic risk factors underlying ARHL, a large whole-genome sequencing (WGS) approach has been carried out in a cohort of 212 cases and controls, both older than 50 years to select genes characterized by a burden of variants specific to cases or controls. Accordingly, the total variation load per gene was compared and two groups were detected: 375 genes more variable in cases and 371 more variable in controls. In both cases, Gene Ontology analysis showed that the largest enrichment for biological processes (fold > 5, p-value = 0.042) was the "sensory perception of sound", suggesting cumulative genetic effects were involved. Replication confirmed 141 genes, while additional analysis based on natural selection led to a prioritization of 21 genes. The majority of them (20 out of 21) showed positive expression in mouse cochlea cDNA and were associated with two functional pathways. Among them, two genes were previously associated with hearing (CSMD1 and PTRPD) and re-sequenced in a large Italian cohort of ARHL patients (N = 389). Results led to the identification of six coding variants not detected in cases so far, suggesting a possible protective role, which requires investigation. In conclusion, we show that this multistep strategy (WGS, selection, expression, pathway analysis and targeted re-sequencing) can provide major insights into the molecular characterization of complex diseases such as ARHL.

10.
Radiol Med ; 123(9): 703-709, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29730840

RESUMO

PURPOSE: To assess the technical feasibility of contrast-enhanced ultrasound (CEUS) in the monitoring of non-infected long bone nonunion healing. METHODS: Twenty-five patients (16 males; mean age: 40.4 ± 11.7) with long bone nonunion were treated using surgery and mesenchymal stem cells and platelet-rich plasma. They performed CEUS up to 15 days before, 7 days, 4 and 8 weeks after treatment. To categorize the angiogenesis around the fracture site, the microvascular blood flow from CEUS was classified into four categories, depending on the portion of the investigated area that was involved in the neovascularization process: grade 0 = 0%; grade 1 = 0-30%; grade 2 = 30-70%; grade 3 = 70-100%. Nonparametric Friedman and Wilcoxon statistics were used. RESULTS: Before treatment, neovascularization was graded as 0 in 15/25 patients, as 1 in 10/25. Vascularity significantly increased over time (P < 0.001), namely: 1 (25th-75th percentile = 1-2) at 7 days; 2 (1-2) at 4 weeks; 3 (0-2) at 8 weeks. All patients but one showed early progressive increase in neovascularization well identified with CEUS at the fracture site. CONCLUSION: CEUS is a feasible method to monitor healing in patients with long bone nonunion.


Assuntos
Meios de Contraste/administração & dosagem , Fraturas Ósseas/diagnóstico por imagem , Fraturas não Consolidadas/diagnóstico por imagem , Neovascularização Fisiológica/fisiologia , Ultrassonografia/métodos , Adulto , Desbridamento , Estudos de Viabilidade , Feminino , Fixação de Fratura/métodos , Fraturas Ósseas/patologia , Fraturas Ósseas/cirurgia , Fraturas não Consolidadas/patologia , Fraturas não Consolidadas/cirurgia , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais , Pessoa de Meia-Idade , Plasma Rico em Plaquetas , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/prevenção & controle , Resultado do Tratamento , Cicatrização
11.
Mol Vis ; 24: 127-142, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29422769

RESUMO

Purpose: To identify genes and genetic markers associated with corneal astigmatism. Methods: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. Results: The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08-1.16), p=5.55×10-9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans-claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). Conclusions: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.


Assuntos
Fosfatase Ácida/genética , Astigmatismo/genética , Claudinas/genética , Doenças da Córnea/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Grupo com Ancestrais do Continente Asiático , Astigmatismo/diagnóstico , Astigmatismo/etnologia , Astigmatismo/patologia , Estudos de Coortes , Córnea/metabolismo , Córnea/patologia , Doenças da Córnea/diagnóstico , Doenças da Córnea/etnologia , Doenças da Córnea/patologia , Grupo com Ancestrais do Continente Europeu , Expressão Gênica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único , Software
12.
J Pediatr Endocrinol Metab ; 30(12): 1257-1263, 2017 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-29127769

RESUMO

BACKGROUND: The association between oxidative stress (OS) and metabolic syndrome (MetS) has been reported in adults. We analyzed the relation between circulating oxidized low-density lipoproteins (Ox-LDL) and MetS in pediatric ages in order to define whether plasma Ox-LDL levels are correlated to obesity and whether oxidative damage, using serum Ox-LDL levels as a proxy, are associated with MetS. METHODS: We enrolled 178 children (11.8±2.6 years). On the basis of a body mass index (BMI) threshold, the subjects were classified as: normal weight BMI <75th percentile; overweight BMI 75-97th percentile; obese BMI >97th percentile. Patients were classified as having MetS if they met three or more of the following criteria for age and sex: BMI >97th percentile, triglyceride levels >95th percentile, high-density lipoprotein (HDL) cholesterol level <5th percentile, systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) >95th percentile and impaired glucose tolerance. RESULTS: Obese children showed increased MetS prevalence (p=0.001) and higher Ox-LDL levels compared to normal- and overweight subjects (p<0.05), with a limited relation between Ox-LDL and MetS (p=0.06). Waist-to-height ratio (W/HtR) (p=0.02), triglycerides (TG) (p=0.001) and LDL-cholesterol (p<0.001) resulted independent predictors of increased plasma Ox-LDL levels. CONCLUSIONS: Oxidative damage was correlated with a hypertriglyceridemic waist phenotype and can be a precocious marker of MetS and cardiometabolic risk in obese children.


Assuntos
Cintura Hipertrigliceridêmica/epidemiologia , Lipoproteínas LDL/sangue , Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , Obesidade Pediátrica/sangue , Obesidade Pediátrica/epidemiologia , Adolescente , Índice de Massa Corporal , Criança , Estudos de Coortes , Feminino , Humanos , Cintura Hipertrigliceridêmica/sangue , Cintura Hipertrigliceridêmica/complicações , Peso Corporal Ideal , Masculino , Síndrome Metabólica/etiologia , Sobrepeso/sangue , Sobrepeso/epidemiologia , Estresse Oxidativo/fisiologia , Obesidade Pediátrica/complicações , Fenótipo , Prevalência , Fatores de Risco
13.
Nat Commun ; 8(1): 910, 2017 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-29030599

RESUMO

Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.


Assuntos
Cadeias alfa de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Estilo de Vida , Lipoproteína(a)/genética , Longevidade/genética , Alelos , Índice de Massa Corporal , Doença das Coronárias/sangue , Doença das Coronárias/etiologia , Educação , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Resistência à Insulina/genética , Lipoproteínas HDL/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Obesidade/complicações , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Fumar/efeitos adversos , Fatores Socioeconômicos
14.
Eat Disord ; 25(3): 216-229, 2017 May-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28139175

RESUMO

This was a retrospective, observational chart review conducted on a convenience sample of 537 outpatients, aged 16-60 years, referred to an Italian Dietetic and Nutrition University Center. The study aimed to look at the association between a history of childhood obesity and dieting behaviors with development of eating disorders (EDs) at a later age. Subjects with a history of EDs (n = 118), assessed using both self-report and health records, were compared with those with no EDs (n = 419), who were attending the clinic mainly for primary prevention of metabolic and cardiovascular risk. Logistic regression analysis was performed to assess the association of childhood-onset obesity with development of an ED at a later age. Childhood-onset obesity, gender, maternal history of eating disorders, and dieting were associated with a positive history of EDs at a later age (p < .05). It is important to raise professional awareness of early symptoms of EDs in children with a history of obesity and treat them accordingly.


Assuntos
Dieta Redutora/estatística & dados numéricos , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Obesidade Pediátrica/epidemiologia , Adolescente , Adulto , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
15.
Springerplus ; 5(1): 1467, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27652042

RESUMO

BACKGROUND: The study evaluated and compared the eating habits and lifestyle of patients with moderate to severe obesity who have undergone Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG). METHODS: Food frequency (FF), food habits (FH), physical activity and life style (PA) as well as smoking habits (SH) were analyzed in 50 RYGB (25 M; aged: 24-64) and 50 SG patients (25 M; aged: 22-63) by means of a validated questionnaire, before (T0) and 6 months (T1) post bariatric surgery. A score for each section (FF, FH, PA, SH) was calculated. RESULTS: ANOVA analysis (age/sex adjusted): FF and FH scores improved at T1 (RYGB and SG: p < 0.001); PA score improved but not significantly; SH score did not change at T1 neither in RYGB nor in SG. Mixed models: FF and PA scores did not correlate with age, gender, weight, BMI, neither in RYGB nor in SG; FH score was negatively correlated both with weight (RYGB: p = 0.002) and BMI (SG: p = 0.003); SH score was positively correlated with age, in SG (p = 0.002); the correlation was stronger in females than in males (p = 0.004). CONCLUSIONS: Although dietary habits improved, patients did not change their physical activity level or their smoking habits. Patients should receive adequate lifestyle counseling to ensure the maximal benefit from bariatric surgery.

16.
Nat Genet ; 47(11): 1352-1356, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26366551

RESUMO

We report sequencing-based whole-genome association analyses to evaluate the impact of rare and founder variants on stature in 6,307 individuals on the island of Sardinia. We identify two variants with large effects. One variant, which introduces a stop codon in the GHR gene, is relatively frequent in Sardinia (0.87% versus <0.01% elsewhere) and in the homozygous state causes Laron syndrome involving short stature. We find that this variant reduces height in heterozygotes by an average of 4.2 cm (-0.64 s.d.). The other variant, in the imprinted KCNQ1 gene (minor allele frequency (MAF) = 7.7% in Sardinia versus <1% elsewhere) reduces height by an average of 1.83 cm (-0.31 s.d.) when maternally inherited. Additionally, polygenic scores indicate that known height-decreasing alleles are at systematically higher frequencies in Sardinians than would be expected by genetic drift. The findings are consistent with selection for shorter stature in Sardinia and a suggestive human example of the proposed 'island effect' reducing the size of large mammals.


Assuntos
Estatura/genética , Variação Genética , Síndrome de Laron/genética , Seleção Genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Transporte/genética , Feminino , Efeito Fundador , Frequência do Gene , Estudo de Associação Genômica Ampla/métodos , Genótipo , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Ilhas , Itália , Canal de Potássio KCNQ1/genética , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Springerplus ; 4: 324, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26180744

RESUMO

The metabolic syndrome (MetS) is a large-scale and expanding public-health and clinical threat worldwide. We investigated the determinants of MetS, assessed its prevalence and components and, estimated their genetic contribution, taking advantage of the special characteristics of Sardinian isolated populations. Inhabitants of 10 villages in Ogliastra region participated in a cross-sectional survey in 2002-2008 (n = 9,647). Blood samples, blood pressure (BP), anthropometry and, data from a standardized interview were collected. Prevalence of MetS was estimated by the direct method of standardization. Variables associated with the MetS were identified using multilevel logistic regression. Heritability was determined using variance component models. MetS Prevalence was 19.6% (95% CI 18.9-20.4%) according to NCEP-ATPIII, 24.8% (95% CI 24.0-25.6%) according to IDF and, 29% (95% CI 28.1-29.8%) according to AHA/NHLBI harmonized criteria, ranging from 9 to 26% among villages. The most prevalent combination was BP + HDL-cholesterol (HDL) + triglycerides (TRIG) (19%), followed by BP + HDL + waist circumference (WAIST) (17%) and, BP + HDL + TRIG + WAIST (13.6%). Heritability of MetS was 48% (p = 1.62 × 10(-25)), as the two most common combinations (BP + HDL + TRIG and BP + HDL + WAIST) showed heritability of 53 and 52%, respectively. The larger genetic components of the two most frequent combinations determining MetS deserve greater investigation in order to understand the underlying mechanisms. Besides, further studies are warranted to confirm these findings both in isolated and outbred populations.

18.
Hum Mol Genet ; 24(19): 5655-64, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26188009

RESUMO

Hearing loss and individual differences in normal hearing both have a substantial genetic basis. Although many new genes contributing to deafness have been identified, very little is known about genes/variants modulating the normal range of hearing ability. To fill this gap, we performed a two-stage meta-analysis on hearing thresholds (tested at 0.25, 0.5, 1, 2, 4, 8 kHz) and on pure-tone averages (low-, medium- and high-frequency thresholds grouped) in several isolated populations from Italy and Central Asia (total N = 2636). Here, we detected two genome-wide significant loci close to PCDH20 and SLC28A3 (top hits: rs78043697, P = 4.71E-10 and rs7032430, P = 2.39E-09, respectively). For both loci, we sought replication in two independent cohorts: B58C from the UK (N = 5892) and FITSA from Finland (N = 270). Both loci were successfully replicated at a nominal level of significance (P < 0.05). In order to confirm our quantitative findings, we carried out RT-PCR and reported RNA-Seq data, which showed that both genes are expressed in mouse inner ear, especially in hair cells, further suggesting them as good candidates for modulatory genes in the auditory system. Sequencing data revealed no functional variants in the coding region of PCDH20 or SLC28A3, suggesting that variation in regulatory sequences may affect expression. Overall, these results contribute to a better understanding of the complex mechanisms underlying human hearing function.


Assuntos
Caderinas/genética , Estudo de Associação Genômica Ampla/métodos , Audição/fisiologia , Proteínas de Membrana Transportadoras/genética , Proteínas do Tecido Nervoso/genética , Animais , Ásia Central , Caderinas/metabolismo , Surdez/genética , Predisposição Genética para Doença , Células Ciliadas Auditivas Internas/metabolismo , Audição/genética , Humanos , Itália , Proteínas de Membrana Transportadoras/metabolismo , Camundongos , Proteínas do Tecido Nervoso/metabolismo , Análise de Sequência de RNA/métodos
20.
Blood ; 124(6): e4-e10, 2014 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-24990887

RESUMO

Abnormalities of platelet size are one of the distinguishing features of inherited thrombocytopenias (ITs), and evaluation of blood films is recommended as an essential step for differential diagnosis of these disorders. Nevertheless, what we presently know about this subject is derived mainly from anecdotal evidence. To improve knowledge in this field, we evaluated platelet size on blood films obtained from 376 patients with all 19 forms of IT identified so far and found that these conditions differ not only in mean platelet diameter, but also in platelet diameter distribution width and the percentage of platelets with increased or reduced diameters. On the basis of these findings, we propose a new classification of ITs according to platelet size. It distinguishes forms with giant platelets, with large platelets, with normal or slightly increased platelet size, and with normal or slightly decreased platelet size. We also measured platelet diameters in 87 patients with immune thrombocytopenia and identified cutoff values for mean platelet diameter and the percentage of platelets with increased or reduced size that have good diagnostic accuracy in differentiating ITs with giant platelets and with normal or slightly decreased platelet size from immune thrombocytopenia and all other forms of IT.


Assuntos
Plaquetas/patologia , Trombocitopenia/sangue , Trombocitopenia/genética , Adolescente , Adulto , Estudos de Casos e Controles , Tamanho Celular , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Perda Auditiva Neurossensorial/sangue , Perda Auditiva Neurossensorial/classificação , Perda Auditiva Neurossensorial/genética , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Proteínas Motores Moleculares/genética , Mutação , Cadeias Pesadas de Miosina/genética , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/diagnóstico , Trombocitopenia/classificação , Trombocitopenia/congênito , Adulto Jovem
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