Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

New evidence suggests that children with chronic conditions may be predisposed to overweight and obesity. This study provides prevalence estimate of obesity for children and adolescents with select chronic conditions. We analyzed reported height and weight and the corresponding BMI from 46,707 subjects aged 10-17 years collected by the National Survey of Children's Health (NSCH-2003). Our main outcome measure was the prevalence of obesity (defined as >/=95th percentile of the sex-specific BMI for age growth charts), adjusted for underlying demographic and socioeconomic factors. We found that the prevalence of obesity among children 10-17 years of age without a chronic condition was 12.2% (95% confidence interval (CI) 11.5-13.0); the prevalence of obesity for children with asthma was 19.7% (19.5-19.9); with a hearing/vision condition was 18.4% (18.2-18.5); with learning disability was 19.3% (19.2-19.4); with autism was 23.4% (23.2-23.6); and with attention-deficit/hyperactivity disorder was 18.9% (18.7-19.0). Our findings suggest that children 10-17 years of age with select chronic conditions were at increased risk for obesity compared to their counterparts without a chronic condition.
Obesity (Silver Spring) 2010 Jan
PMID:Prevalence of obesity among children with chronic conditions. 1952 50

We hypothesize that when two pathological conditions or personality traits share the same critical period for gene-environment interaction, we should expect further similarities, particularly from clinical and pathophysiological perspectives. They should therefore be considered as two facets of the same disease. To test this hypothesis we compiled data included in the Primal Health Research Database. This database (www.primalhealthresearch.com) is specialised in studies exploring correlations between what happens during the 'primal period' (fetal life, perinatal period and year following birth) and what happens later on in life in terms of health and personality traits. After mentioning the links between autism and anorexia nervosa, we explore more in depth the links between attention deficit hyperactivity disorder (ADHD) and obesity. We suggest from such examples that the nature of an environmental factor is often less important than the timing of the interaction. We conclude that the concept of gene expression, combined with Primal Health Research, might lead to reconsider conventional nosological classifications. Some previously well-defined pathological entities should be included into the framework of multifaceted diseases. On the other hand some existing pathological entities should be dismantled.
 ...
PMID:Attention deficit hyperactivity disorder (ADHD) and obesity: two facets of the same disease? 1966 51

Meta-analysis of genomic coordinates of SNP variations identified in genome-wide association studies (GWAS) of up to 712,253 samples (comprising 221,158 disease cases, 322,862 controls, and 168,233 case/control subjects of obesity GWAS) reveals that 39% of SNPs associated with 22 common human disorders are located within intergenic regions. Chromatin-state maps based on H3K4me3-H3K36me3 signatures show that many intergenic disease-linked SNPs are located within the boundaries of the K4-K36 domains, suggesting that SNP-harboring genomic regions are transcribed. Here we report identification of 13 trans-regulatory RNAs (transRNAs) 100 to 200 nucleotides in length containing intergenic SNP sequences associated with Crohn's disease, rheumatoid arthritis, type 1 diabetes, vitiligo, hypertension and multiple types of epithelial malignancies (prostate, breast, ovarian and colorectal cancers). We demonstrate that NALP1 loci intergenic SNP sequence, rs2670660, is expressed in human cells and may contribute to clinical manifestations of autoimmune and autoimflammatory phenotypes by generating distinct allelic variants of transRNAs. Stable expression of allele-specific sense and anti-sense variants of transRNAs markedly alters cellular behavior, affect cell cycle progression, and interfere with monocyte/macrophage transdifferentiation. On a molecular level, forced expression of allele-specific sense and anti-sense variants of transRNAs asserts allele-specific genome-wide effects on abundance of hundreds microRNAs and mRNAs. Using lentiviral gene transfer, microarray and Q-RT-PCR technologies, we identify rs2670660 allele-specific gene expression signatures (GES) which appear useful for detecting the activated states of innate immunity/inflammasome pathways in approximately 700 clinical samples from 185 control subjects and 350 patients diagnosed with nine common human disorders, including Crohn's disease, ulcerative colitis, rheumatoid arthritis, Huntington disease, autism, Alzheimer disease, obesity, prostate and breast cancers. Microarray analysis of clinical samples demonstrates that rs2670660 allele-specific GES are engaged in patients' peripheral blood mononuclear cells (PBMC) which encounter pathological conditions in coherent tissues of a human body during immune surveillance and homeostasis monitoring. These data indicate that expression of transRNAs encoded by specific intergenic sequences can trigger activation of innate immunity/inflammasome pathways and contribute to clinical development of autoinflammatory and autoimmune syndromes. Documented in this work single-base substitution-driven molecular and biological antagonisms of intergenic SNP-containing transRNAs suggest a guiding mechanism of selection and retention of phenotype-compatible intergenic variations during evolution. According to this model, random genetic variations which generate transRNAs asserting antagonistic phenotype-altering effects compared to ancestral alleles will be selected and retained as SNP variants.
 ...
PMID:Identification of intergenic trans-regulatory RNAs containing a disease-linked SNP sequence and targeting cell cycle progression/differentiation pathways in multiple common human disorders. 1992 86

Obesity is a highly heritable and genetically heterogeneous disorder. Here we investigated the contribution of copy number variation to obesity in 300 Caucasian patients with severe early-onset obesity, 143 of whom also had developmental delay. Large (>500 kilobases), rare (<1%) deletions were significantly enriched in patients compared to 7,366 controls (P < 0.001). We identified several rare copy number variants that were recurrent in patients but absent or at much lower prevalence in controls. We identified five patients with overlapping deletions on chromosome 16p11.2 that were found in 2 out of 7,366 controls (P < 5 x 10(-5)). In three patients the deletion co-segregated with severe obesity. Two patients harboured a larger de novo 16p11.2 deletion, extending through a 593-kilobase region previously associated with autism and mental retardation; both of these patients had mild developmental delay in addition to severe obesity. In an independent sample of 1,062 patients with severe obesity alone, the smaller 16p11.2 deletion was found in an additional two patients. All 16p11.2 deletions encompass several genes but include SH2B1, which is known to be involved in leptin and insulin signalling. Deletion carriers exhibited hyperphagia and severe insulin resistance disproportionate for the degree of obesity. We show that copy number variation contributes significantly to the genetic architecture of human obesity.
 ...
PMID:Large, rare chromosomal deletions associated with severe early-onset obesity. 2088 Jan 23

Neurotrophins, particularly, NGF and BDNF are now well recognized to mediate a dizzying number of trophobiological effects, ranging from the Rita Levi-Montalcini's neurotrophic through immunotrophic to metabotrophic effects.These are implicated in the pathogenesis of various diseases including neuropsychiatric and cardiometabolic diseases, such as dementia, depression, type 2 diabetes and obesity that may express a common phenotype and coexistence. Recently, adipobiology (adiposcience) as become a focus of numerous studies showing that the adipose tissue is the body's largest endocrine organ producing multiple signaling proteins, including NGF and BDNF, all these dubbed adipokines. On the basis of our and other authors' evidence that low NGF and/or BDNF levels are found in cardiometabolic diseases (atherosclerosis, obesity, type 2 diabetes, metabolic syndrome), a hypothesis of a critical role of neuro-metabotrophic deficit in the pathogenesis of these diseases has been raised. Since NGF and BDNF also exerts various synaptotrophic effects involved in cognitive enhancement, this hypothesis might also be related to neuropsychiatric diseases such as dementia, depression, schizophrenia, autism, Rett syndrome, anorexia nervosa, and bulimia nervosa. Finally, NGF- and BDNF-based therapeutic approach, including ampakines, antidepressants, selective deacetylase inhibitors, statins, peroxisome proliferator-activated receptor gamma agonists, and "brain food" and calorie restriction, is outlined.
 ...
PMID:NGF and BDNF: from nerves to adipose tissue, from neurokines to metabokines. 2006 8

Parents of children with autism often report gastrointestinal problems as well as picky eating and selective eating in their children. The purpose of this study was to evaluate the nutritional status and the nutrient intake in 111 Chinese children with autism, aged between 2 and 9 years. Anthropometric data were expressed as Z scores. A 3-day dietary recall was provided by the parents, and the data were compared with the national Dietary Reference Intakes (DRI) standards for Chinese children. The results showed that only nine of the autistic children (8.1%) were acute or chronically malnourished. From the remaining 102 patients, 67 (60.4%) were eutrophic and 35 (31.5%) had either overweight or obesity. Intakes of both calories and proteins were adequate in the vast majority of these children, but the calories from fat was lower than DRI in the same age group. The average intake of vitamin E and niacin exceeded 100% of DRI, and the intakes of vitamin B1 and B2, magnesium, and iron were between 80% and 90% of DRI range. However, the following nutrients did not meet the DRI requirements at all: vitamins A, B6 and C, folic acid, calcium, and zinc. Although growth was satisfactory in the vast majority of these children with autistic disorder, this study revealed serious deficiencies in the intakes of several vitamins and essential nutrients.
 ...
PMID:A preliminary study on nutritional status and intake in Chinese children with autism. 2042 15

The 15q11-q13 PWS/AS critical region involves genes that are characterized by genomic imprinting. Multiple repeat elements within the region mediate rearrangements, including interstitial duplications, interstitial triplications, and supernumerary isodicentric marker chromosomes, as well as the deletions that cause Prader-Willi syndrome (PWS) and Angelman syndrome (AS). Recently, duplications of maternal origin concerning the same critical region have been implicated in autism spectrum disorders (ASD). We present a 6-month-old girl carrying a de novo duplication of maternal origin of the 15q11.2-q14 PWS/AS region (17.73 Mb in size) [46,XX,dup(15)(q11.2-q14)] detected with a high-resolution microarray-based comparative genomic hybridization (array-CGH). The patient is characterized by severe hypotonia, obesity, microstomia, long eyelashes, hirsutism, microretrognathia, short nose, severe psychomotor retardation, and multiple episodes of drug-resistant epileptic seizures, while her brain magnetic resonance imaging (MRI) documented partial corpus callosum dysplasia. In our patient the duplicated region is quite large extending beyond the Prader-Willi-Angelman critical region (PWACR), containing a number of genes that have been shown to be involved in ASD, exhibiting a severe phenotype, beyond the typical PWS/AS clinical manifestations. Reporting of similar well-characterized clinical cases with clearly delineated breakpoints of the duplicated region will clarify the contribution of specific genes to the phenotype.
 ...
PMID:De novo interstitial duplication of the 15q11.2-q14 PWS/AS region of maternal origin: Clinical description, array CGH analysis, and review of the literature. 2057 9

Genomically imprinted genes show parentally fixed mono-allelic expression and are important for the mammalian development. Dysregulation of genomic imprinting leads to several complex pathological conditions. Though the genetic and epigenetic regulation of imprinted genes has been well studied, their protein aspects are largely ignored. Here, we systematically studied a sub-network centered on proteins encoded by imprinted genes within human interactome. Using concepts of network biology, we uncover a highly connected, transitive and central network module of imprinted gene-products and their interacting partners (IGPN). The network is enriched in development, metabolism and cell cycle related functions and its malfunctioning ascribes error intolerance to human interactome network. Further, detailed analysis revealed that its higher centrality is determined by 'date' interactions among the proteins belonging to different functional classes than the 'party' interactions within the same functional class. Interestingly, a significant proportion of this network genetically associates with disease phenotypes. Moreover, the network comprises of gene-sets that are upregulated in leukemia, psychosis, obesity/diabetes and downregulated in autism. We conclude that imprinted gene-products are part of a functionally and topologically important module of human interactome and errors in this sub-network are intolerant to, otherwise robust, human interactome. The findings might also shed light on how imprinted genes, which are rather very few, coordinate at protein level to pleiotropically regulate growth and metabolism during embryonic and post-natal development.
 ...
PMID:Systems properties of proteins encoded by imprinted genes. 2067 38

For more than a century, clinical investigators have focused on early life as a source of adult psychopathology. Early theories about psychic conflict and toxic parenting have been replaced by more recent formulations of complex interactions of genes and environment. Although the hypothesized mechanisms have evolved, a central notion remains: early life is a period of unique sensitivity during which experience confers enduring effects. The mechanisms for these effects remain almost as much a mystery today as they were a century ago. Recent studies suggest that maternal diet can program offspring growth and metabolic pathways, altering lifelong susceptibility to diabetes and obesity. If maternal psychosocial experience has similar programming effects on the developing offspring, one might expect a comparable contribution to neurodevelopmental disorders, including affective disorders, schizophrenia, autism, and eating disorders. Due to their early onset, prevalence, and chronicity, some of these disorders, such as depression and schizophrenia, are among the highest causes of disability worldwide according to the World Health Organization 2002 report. Consideration of the early life programming and transcriptional regulation in adult exposures supports a critical need to understand epigenetic mechanisms as a critical determinant in disease predisposition. Incorporating the latest insight gained from clinical and epidemiological studies with potential epigenetic mechanisms from basic research, the following review summarizes findings from a workshop on Early Life Programming and Neurodevelopmental Disorders held at the University of Pennsylvania in 2009.
 ...
PMID:Early life programming and neurodevelopmental disorders. 2067 2

Sleeping disorders are frequently encountered in infants and adolescents. They often induce a distress in the family, an individual sadness possibly leaving at time to maltreatment. In the normal infant or the medically fragile infant due to prematurity or an acute episode, complaints from the patient or family sources force the medical team to find an explanation or a treatment, which are not always adequate. In other conditions such as asthma, obesity, anorexia nervosa, autism, cerebral palsy, hyperactivity, the sleeping disorders may be so unnoticed or remain insufficiently investigated. Globally, in this domain, the clinical description is often imprecise and sleep studies underused. A more accurate assessment should lead to a better educative approach and more appropriate therapy.
 ...
PMID:[Inertia or overtreatment in children. When sleeping time is disturbed in infants: how to improve the family's distress]. 2068 23


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>