Known single gene polymorphisms significantly contribute to human obesity
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Peer-reviewed literature and clinical studies confirm that specific single nucleotide polymorphisms, such as those in the FTO and MC4R genes, are associated with obesity susceptibility and contribute to the heritable component of human body fatness.
Obesity has become a global epidemic and contributes to the increasing burden of type 2 diabetes, cardiovascular disease, stroke, some types of cancer, and premature death worldwide. Obesity is highly heritable and arises from the interactions of multiple genes, environmental factors, and behavior. In this paper, the authors reviewed recent developments in genetic epidemiologic research, focusing particularly on several promising genomic regions and obesity-related genes. Gene-gene and gene-environment interactions of obesity were also discussed. Published studies were accessed through the MEDLINE database. The authors also searched the Obesity Gene Map Database (http://obesitygene.pbrc.edu/) and conducted a manual search using references cited in relevant papers. Heritabilities for obesity-related phenotypes varied from 6% to 85% among various populations. As of October 2005, 253 quantitative trait loci for obesity-related phenotypes have been localized in 61 genome-wide linkage scans, and genetic variants in 127 biologic candidate genes have been reported to be associated with obesity-related phenotypes from 426 positive findings. Gene-gene interactions were also observed in several genes, and some genes were found to influence the effect of dietary intake and physical activity on obesity-related phenotypes. Integration of genetic epidemiology with functional genomics and proteomics studies will be required to fully understand the role of genetic variants in the etiology and prevention of obesity.
Objectives Bitter taste perception affects food preference, eating behavior, and nutrient intake. The purpose of this study was to investigate the contribution of bitter taste gene polymorphisms to body fatness as measured by percentage of body fat. Method Three common single nucleotide polymorphisms (SNPs) of the TAS2R38 gene which result in amino acid changes in the protein (A49P, V262A, and I296V), were studied in three racially diverse groups: European Americans n = 313, African Americans n = 109, and Asians n = 234. Results The allele frequencies of the three SNPs were similar to previous studies. The rare haplotypes, AAI and AAV, were found in high prevalence in the African American subgroup (22.94%) and European American subgroup (6.07%). The PROP non taster; AVI/AVI diplotype was associated with a higher risk of obesity in European American and Asian but not African American subjects after age adjustment. Conclusions TAS2R38 polymorphisms could be associated with obesity development. In addition to taste perception, nutrient sensing and energy metabolism should be studied in relation to bitter taste receptors to confirm the association between genetic polymorphisms and body fatness. Genetic polymorphisms, race, gender, and environmental factors such as dietary patterns could all contribute to body fat.
Genetics of Obesity in Chinese Youngs
The purpose of this study is to explore the pathogenesis and genetic susceptibility of obese subjects,providing a convincing argument for further treatment of obesity and metabolic syndrome. Obesity has become a major worldwide challenge to public health, owing to an interaction between the obesogenic environment and a strong genetic contribution.Previous studies found that genetic factors determine 40%-70% of obese phenotype.Under such circumstances, the screening of obesity susceptibility gene is particularly important for society or family to take measures to prevent obesity. Recent extensive genome-wide association studies(GWASs) have identified numerous single nucleotide polymorphisms associated with obesity,but these loci together account for only a small fraction of the known heritable component.Two studies in 2010 Nature,for the first time, put rare copy number variation (CNV)in association with severe early-onset obesity.Their significance lie not only in the discovery of the pathogenic genes of severe early-onset obesity but,more importantly,in providing new strategies for finding out genes that cause complex diseases.
Mutations of the melanocortin-4 receptor (MC4R) gene are associated with the appetite, obesity and growth in pig, mice and human. But little is known about the function of chicken MC4R gene. In this study, F2 chicken resource population derived from broilers crossing to Silky was screened for the polymorphisms of the MC4R gene using PCR-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing methods. Four single nucleotide polymorphisms (SNPs) sites were found. The mutation (C --> T) in the 5' regulation region of chicken MC4R gene results in one more NF-E2 and cap transcription factor binding sites in the mutation allele than in the wild allele. One missense mutation (G --> A) occurs in the coding region (61nt), which changes the glycine to arginine. Moreover, in the coding region there are 2 synonymous mutations, one G --> T mutation at 315nt and one C --> T mutation at 336nt. Least square analysis of the SNPs and carcass traits showed that BB, DD and FF genotypes are significantly associated with body weight, carcass weight (or half carcass weight), and leg muscle weight (P < 0.05 or P < 0.01). But no significant association between the genotypes and abdominal fat weight is found. The results present the evidence that the chicken MC4R gene can be selected as the major candidate gene for the carcass traits such as body weight and growth.
Particular objective of the project is providing an answer to the question: Are type 1 diabetic children who are carriers of the AA genotype of the FTO gene polymorphism (rs9939609) at risk of more weight gain in the course of insulin therapy when compared to carriers of the TA and TT genotypes of this polymorphism ? Background: Gene polymorphism including some genetic variants may predispose to the development of cardiovascular diseases and their complications. A great advance in studies on genetic susceptibility to obesity was the discovery of the gene called FTO - fat mass and obesity associated gene. The A allele of the FTO gene predisposing to obesity occurs in approximately 40% of the European population and each copy of this allele can increase BMI by 0.1 Z-score i.e. by 0.4 kg/m2. However, there are very few data on the impact of human genome on body weight change following particular intervention. An important problem to be dealt with by physicians and type 1 diabetic patients is overweight and obesity. This problem is inevitably associated with insulin therapy and excess energy intake. Insulin therapy in diabetic patients may result in excess body weight gain.
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