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      The Effects of Genetic Variation in FTO rs9939609 on Obesity and Dietary Preferences in Chinese Han Children and Adolescents

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          Abstract

          The association of the rs9939609 single nucleotide polymorphism in FTO gene with obesity has been extensively investigated in studies of populations of European, African, and Asian ancestry. However, inconsistent results have been reported in Asian populations, and the relationship of FTO variation and dietary behaviors has only rarely been examined in Chinese children and adolescents. The aim of this study was to assess the association of rs9939609 with obesity and dietary preferences in childhood in a Chinese population. Epidemiological data including dietary preferences were collected in interviews using survey questionnaires, and rs9939609 genotype was determined by real-time PCR. The associations of rs9939609 genotypes with obesity and dietary preferences were analyzed by multivariate logistic regression using both additive and dominant models. The results showed that subjects with a TA or AA genotype had an increased risk of obesity compared with the TT participants; the odds ratios (ORs) were 1.47 (95% CI: 1.25–1.71, P = 1.73×10 −6), and 3.32 (95% CI: 2.01–5.47, P = 2.68×10 −6), respectively. After adjusting for age and gender, body mass index, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, triglycerides, and low-density lipoprotein cholesterol were higher, and high-density lipoprotein cholesterol was lower in TA and AA participants than in those with the TT genotype. After additionally controlling for body mass index, the association remained significant only for systolic blood pressure ( P = 0.005). Compared with TT participants, those with the AA genotype were more likely to prefer a meat-based diet (OR = 2.81, 95% CI: 1.52–5.21). The combined OR for obesity in participants with TA/AA genotypes and preference for a meat-based diet was 4.04 (95% CI: 2.8–5.81) compared with the TT participants who preferred a plant-based diet. These findings indicate the genetic variation of rs9939609 is associated with obesity and dietary preferences in Chinese children and adolescents.

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          Most cited references56

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          Childhood obesity: public-health crisis, common sense cure

          The Lancet, 360(9331), 473-482
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            An obesity-associated FTO gene variant and increased energy intake in children.

            Variation in the fat mass and obesity-associated (FTO) gene has provided the most robust associations with common obesity to date. However, the role of FTO variants in modulating specific components of energy balance is unknown. We studied 2726 Scottish children, 4 to 10 years of age, who underwent genotyping for FTO variant rs9939609 and were measured for height and weight. A subsample of 97 children was examined for possible association of the FTO variant with adiposity, energy expenditure, and food intake. In the total study group and the subsample, the A allele of rs9939609 was associated with increased weight (P=0.003 and P=0.049, respectively) and body-mass index (P=0.003 and P=0.03, respectively). In the intensively phenotyped subsample, the A allele was also associated with increased fat mass (P=0.01) but not with lean mass. Although total and resting energy expenditures were increased in children with the A allele (P=0.009 and P=0.03, respectively), resting energy expenditure was identical to that predicted for the age and weight of the child, indicating that there is no defect in metabolic adaptation to obesity in persons bearing the risk-associated allele. The A allele was associated with increased energy intake (P=0.006) independently of body weight. In contrast, the weight of food ingested by children who had the allele was similar to that in children who did not have the allele (P=0.82). The FTO variant that confers a predisposition to obesity does not appear to be involved in the regulation of energy expenditure but may have a role in the control of food intake and food choice, suggesting a link to a hyperphagic phenotype or a preference for energy-dense foods. 2008 Massachusetts Medical Society
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              Obesity associated genetic variation in FTO is associated with diminished satiety.

              Polymorphisms within the FTO gene have consistently been associated with obesity across multiple populations. However, to date, it is not known whether the association between genetic variation in FTO and obesity is mediated through effects on energy intake or energy expenditure. Our objective was to examine the association between alleles of FTO known to increase obesity risk and measures of habitual appetitive behavior. The intronic FTO single nucleotide polymorphism (rs9939609) was genotyped in 3337 United Kingdom children in whom measures of habitual appetitive behavior had been assessed using two scales (Satiety Responsiveness and Enjoyment of Food) from the Child Eating Behaviour Questionnaire, a psychometric tool that has been validated against objective measures of food intake. Associations of FTO genotype with indices of adiposity and appetite were assessed by ANOVA. As expected, the A allele was associated with increased adiposity in this cohort and in an independent case-control replication study of United Kingdom children of similar age. AA homozygotes had significantly reduced Satiety Responsiveness scores (P = 0.008, ANOVA). Mediation analysis indicated that the association of the AA genotype with increased adiposity was explained in part through effects on Satiety Responsiveness. We have used a unique dataset to examine the relationship between a validated measure of children's habitual appetitive behavior and FTO obesity risk genotype and conclude that the commonest known risk allele for obesity is likely to exert at least some of its effects by influencing appetite.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                11 August 2014
                : 9
                : 8
                : e104574
                Affiliations
                [1 ]Department of Nutrition, Zhejiang University School of Public Health, Hangzhou, China
                [2 ]Department of Epidemiology & Biostatistics, Zhejiang University School of Public Health, Hangzhou, China
                [3 ]Hangzhou Center for Disease Control and Prevention, Hangzhou, China
                [4 ]Department of Pediatrics, the First Affiliated Hospital of College of Medicine, Zhejiang University, Hangzhou, China
                [5 ]Department of Endocrinology, Children's Hospital of College of Medicine, Zhejiang University, Hangzhou, China
                [6 ]Department of Endocrinology, Children's Hospital Affiliated to Chongqing Medical University, Chongqing, China
                [7 ]Department of Pediatrics, General Hospital of Tianjin Medical University, Tianjin, China
                [8 ]Beijing Children's Hospital Affiliated to Capital Medical University, Beijing, China
                [9 ]Department of Pediatric Endocrinology and Inborn Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China
                [10 ]Department of Pediatrics Endocrinology, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
                [11 ]Department of Pathology, Zhejiang University School of Medicine, Hangzhou, China
                University of Pennsylvania Perelman School of Medicine, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: YZ. Performed the experiments: LL JF FX GL CG FL SC CX DZ ZL SZ YZ HW. Analyzed the data: MY YX. Wrote the paper: MY. Revised the manuscript: MY YZ.

                Article
                PONE-D-13-23342
                10.1371/journal.pone.0104574
                4128666
                25919024
                9b6fb126-00d3-46b0-86bd-69ed0222ed02
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 5 June 2013
                : 15 July 2014
                Page count
                Pages: 9
                Funding
                This study has been supported by National Key Technology R&D Program of China (2012BAI02B03, 2009BAI80B02), Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents, Fundamental Research Funds for the Central Universities and Program for Zhejiang Leading Team of Science and Technology Innovation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Computational Biology
                Evolutionary Biology
                Population Genetics
                Genetic Polymorphism
                Genetics
                Nutrition
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Population Biology
                Medicine and Health Sciences
                Epidemiology
                Genetic Epidemiology
                Pediatric Epidemiology

                Uncategorized
                Uncategorized

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