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Article |

Attenuation of the Effect of the FTO rs9939609 Polymorphism on Total and Central Body Fat by Physical Activity in Adolescents:  The HELENA Study FREE

Jonatan R. Ruiz, PhD; Idoia Labayen, PhD; Francisco B. Ortega, PhD; Vanessa Legry, PhD; Luis A. Moreno, MD, PhD; Jean Dallongeville, MD, PhD; David Martínez-Gómez, BSc; Szilvia Bokor, MD, PhD; Yannis Manios, PhD; Donatella Ciarapica, PhD; Frederic Gottrand, MD, PhD; Stefaan De Henauw, MD, PhD; Denes Molnár, MD, PhD; Michael Sjöström, MD, PhD; Aline Meirhaeghe, PhD; HELENA Study Group
[+] Author Affiliations

Author Affiliations: Unit for Preventive Nutrition, Department of Biosciences and Nutrition at NOVUM, Karolinska Institutet, Huddinge, Sweden (Drs Ruiz, Ortega, and Sjöström); Department of Nutrition and Food Science, University of the Basque Country, Vitoria, Spain (Dr Labayen); Department of Physiology, University of Granada, Granada, Spain; Institut National de la Santé et la Recherche Médicale Unit 744, Institut Pasteur de Lille, Université Lille Nord de France, and Université Droit et Santé de Lille (Drs Legry, Dallongeville, Bokor, and Meirhaeghe) and Department of Medicine, University of Lille, and Department of Pediatrics, Jeanne de Flandre Children's University Hospital (Dr Gottrand), Lille, France; Growth, Exercise, Nutrition, and Development Research Group, University School of Health Sciences, University of Zaragoza, Zaragoza, Spain (Dr Moreno); Immunonutrition Research Group, Department of Metabolism and Nutrition, Instituto del Frío, Institute of Food Science, Technology, and Nutrition, Spanish National Research Council, Madrid, Spain (Mr Martínez-Gómez); Department of Nutrition and Dietetics, Harokopio University, Athens, Greece (Dr Manios); National Research Institute for Food and Nutrition, Roma, Italy (Dr Ciarapica); Department of Public Health, Ghent University Hospital, Ghent, Belgium (Dr De Henauw); and Department of Pediatrics, University of Pécs, Pécs, Hungary (Dr Molnár).


Arch Pediatr Adolesc Med. 2010;164(4):328-333. doi:10.1001/archpediatrics.2010.29.
Text Size: A A A
Published online

Objective  To examine whether physical activity attenuates the effect of the FTO rs9939609 polymorphism on body fat estimates in adolescents.

Design  Cross-sectional study.

Setting  Athens, Greece; Dortmund, Germany; Ghent, Belgium; Heraklion, Greece; Lille, France; Pécs, Hungary; Rome, Italy; Stockholm, Sweden; Vienna, Austria; and Zaragoza, Spain, from October 2006 to December 2007.

Participants  Adolescents from the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study (n = 752).

Main Exposure  Physical activity.

Main Outcome Measures  The FTO rs9939609 polymorphism was genotyped. Physical activity was assessed by accelerometry. We measured weight, height, waist circumference, and triceps and subscapular skinfolds; body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]) and body fat percentage were calculated.

Results  The A allele of the FTO polymorphism was significantly associated with higher BMI (+0.42 per risk allele), higher body fat percentage (+1.03% per risk allele), and higher waist circumference (+0.85 cm per risk allele). We detected significant or borderline gene × physical activity interactions for the studied body fat estimates (for interaction, P = .02, .06, and .10 for BMI, body fat percentage, and waist circumference, respectively). Indeed, the effect of the FTO rs9939609 polymorphism on these body fat parameters was much lower in adolescents who met the daily physical activity recommendations (ie, ≥60 min/d of moderate to vigorous physical activity) compared with those who did not: +0.17 vs +0.65 per risk allele in BMI, respectively; +0.40% vs +1.70% per risk allele in body fat percentage, respectively; and +0.60 vs +1.15 cm per risk allele in waist circumference, respectively.

Conclusion  Adolescents meeting the daily physical activity recommendations may overcome the effect of the FTO rs9939609 polymorphism on obesity-related traits.

Figures in this Article

There is compelling evidence that human obesity is a multifactorial disorder where both genes1,2 and lifestyle factors, including diet and physical activity,3,4 are important contributors. Among the obesity-related genes, polymorphisms in the fat mass– and obesity-associated gene (FTO) are strongly associated with body fat estimates in populations of different ethnic backgrounds or ages.510 It was estimated that each copy of the FTO rs9939609 minor allele (ie, A allele) corresponds to approximately 1.5-kg–heavier body weight, and the prevalence of this risk allele in white individuals is around 40%.6

Several studies suggested that the deleterious effect of the FTO polymorphism could be attenuated by physical activity,1113 whereas others were not able to show such effect.1416 These studies were mainly focused on adult populations and all assessed physical activity by means of self-reported questionnaires. One study in 438 adolescents aged 15 years failed to detect an interaction between the FTO rs9939609 polymorphism and self-reported physical activity.16

The US Department of Health and Human Services recently released physical activity guidelines for youth.17 They suggested that children and adolescents should participate in physical activity for 60 min/d or longer, and most of the activity should be of moderate to vigorous intensity.

The goals of our study were to investigate the interaction between the FTO rs9939609 polymorphism and physical activity objectively assessed by accelerometry on body mass index (BMI), body fat percentage, and waist circumference and to assess whether meeting the daily physical activity recommendations could abolish the deleterious effect of the FTO rs9939609 polymorphism on body fat estimates in a cohort of European adolescents.

PARTICIPANTS

Adolescents were part of the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study (HELENA-CSS). The HELENA-CSS was designed to obtain reliable and comparable data on nutrition and health-related parameters of a sample of European adolescents.18,19 A total of 3865 adolescents were recruited between October 2006 and December 2007. Adolescents were randomly selected from schools using a proportional cluster sampling taking into account geographical distribution in each city, private/public school ratio, and number of classes by school. One-third of the classes were randomly selected for blood collection, resulting in a total of 1155 blood samples for the subsequent clinical biochemistry assays and genetic analyses. Among these participants, 752 adolescents (413 girls) with data on FTO rs9939609, BMI, and physical activity were included in this study (namely, the final sample). The 2 samples (the “blood” sample and the “final” sample) were similar in terms of genotype frequencies (TT: 37.9 vs 36.6, respectively; TA: 45.5 vs 47.1, respectively; and AA: 16.7 vs 16.4, respectively; P = .87) and levels of moderate to vigorous physical activity (mean [SD], 45.6 [17.7] vs 40.4 [14.0] min/d, respectively; P = .41), whereas the BMIs were different (mean [SD], 22.7 [5.6] vs 21.7 [6.8], respectively; P < .001). After receiving complete information about the aims and methods of the study, all adolescents and their parents or guardians were fully informed and signed an informed written consent. All participants met the general HELENA-CSS inclusion criteria.18,19 The study was performed following the ethical guidelines of the Declaration of Helsinki 1961 (revision of Edinburgh 2000), Good Clinical Practice, and legislation about clinical research in humans in each of the participating countries. The protocol was approved by the corresponding local human research review committees of the centers involved.20

ASSESSMENT OF BODY FAT

Weight and height were measured following standard procedures,21 and BMI was calculated as weight in kilograms divided by height in meters squared. Waist circumference was measured in triplicate at the midpoint between the superior iliac spine and the costal edge in the midaxillary line with an anthropometric unelastic tape (SECA 200; Seca Deutschland, Hamburg, Germany) and was used as a surrogate measure of central body fat. It was recorded to the nearest 0.1 cm. Skinfold thickness was measured to the nearest 0.2 mm in triplicate on the left side at the biceps, triceps, subscapularis, suprailium, thigh, and medial calf with a Holtain Caliper (Holtain Ltd, Crymmych, Wales).21 Body fat percentage was calculated from skinfold thicknesses (triceps and subscapularis) using the equations by Slaughter et al.22

ASSESSMENT OF PUBERTAL STATUS

Pubertal stage was recorded by a trained researcher of the same sex as the child, according to Tanner and Whitehouse23 and as described elsewhere.24

ASSESSMENT OF PHYSICAL ACTIVITY

Physical activity was assessed during 7 consecutive days with a uniaxial accelerometer (GT1M; ActiGraph, Pensacola, Florida) attached to the lower back. Adolescents were instructed to wear the accelerometer during all time awake and to remove it only during water-based activities. At least 3 days of recording with a minimum of 8 hours registered per day was set as an inclusion criterion. The time-sampling interval (epoch) was set at 15 seconds.25 We calculated the time engaged in at least moderate physical activity (≥3 metabolic equivalents) based on a standardized cutoff of 2000 counts/min or more. Moderate to vigorous physical activity was dichotomized into less than 60 min/d and 60 min/d or longer.17,26

GENOTYPING

The FTO rs9939609 genotyping was done by an Illumina system (Illumina, Inc, San Diego, California) using the GoldenGate technology (GoldenGate Software, Inc, San Francisco, California). The genotyping success rate was 100%. The genotype distribution respected Hardy-Weinberg equilibrium (P = .56).

STATISTICAL ANALYSIS

The genotypes were coded as an ordinal variable (ie, 0 = TT, 1 = TA, 2 = AA). We analyzed the differences in body fat estimates (BMI, body fat percentage, and waist circumference) between the 3 FTO rs9939609 genotypes with an additive model using a mixed-effects linear regression model with random intercept allowing the center effects to be random and with age and sex as potential confounders (fixed effects). To test for the existence of an interaction between the FTO rs9939609 polymorphism and moderate to vigorous physical activity (<60 min/d and ≥60 min/d) on body fat estimates (BMI, body fat percentage, and waist circumference), we used the same model but added the cross-product term FTO × physical activity. Finally, we repeated the analyses stratified by moderate to vigorous physical activity categories (<60 min/d and ≥60 min/d of moderate to vigorous physical activity).

Analyses were performed using SPSS version 16.0 statistical software for Windows (SPSS Inc, Chicago, Illinois). The level of significance was set to .05 for all but the interaction effect, which was considered to .10.

Characteristics of the study sample are shown in the Table. Genotype frequencies were 275 (0.37%), 354 (0.47%), and 123 (0.16%) for the TT, TA, and AA genotypes, respectively.

Table Graphic Jump LocationTable. Characteristics of the Study Cohort
ASSOCIATION BETWEEN THE FTO rs9939609 POLYMORPHISM AND BODY FAT ESTIMATES

We observed that the minor A allele of the FTO polymorphism was significantly associated with higher BMI (+0.42 per risk allele; 95% confidence interval [CI], 0.10 to 0.75; P = .01), higher body fat percentage (+1.03% per risk allele; 95% CI, 0.19 to 1.88; P = .02), and higher waist circumference (+0.85 cm per risk allele; 95% CI, 0.04 to 1.66; P = .04) after adjusting for age, sex, and center (Figure 1).

Place holder to copy figure label and caption
Figure 1.

Association between the FTO polymorphism rs9939609 and mean body mass index (calculated as weight in kilograms divided by height in meters squared), body fat percentage, and waist circumference. Error bars indicate 95% confidence intervals. Values are adjusted for center, sex, and age.

Graphic Jump Location
INTERACTION BETWEEN THE FTO rs9939609 POLYMORPHISM AND PHYSICAL ACTIVITY

We did not observe significant differences among the FTO genotypes in time spent participating in moderate to vigorous physical activity (mean [SD], 61.2 [24.1], 57.1 [23.2], and 60.1 [24.3] min/d for the TT, TA, and AA genotypes, respectively; P = .54). We observed significant interactions between the FTO polymorphism and physical activity (<60 and ≥60 min/d of moderate to vigorous physical activity) when considering BMI (for interaction, P = .02), body fat percentage (for interaction, P = .06), or waist circumference (for interaction, P = .10). Indeed, in those adolescents who spent less than 60 min/d participating in moderate to vigorous physical activity (n = 441 [59%]), the A allele of the FTO polymorphism was significantly associated with higher BMI (+0.65 per risk allele; 95% CI, 0.21 to 1.10; P = .005), higher body fat percentage (+1.70% per risk allele; 95% CI, 0.58 to 2.81; P = .003), and higher waist circumference (+1.15 cm per risk allele; 95% CI, 0.04 to 2.26; P = .04) after adjusting for center, sex, and age (Figure 2). In contrast, in those adolescents who spent at least 60 min/d participating in moderate to vigorous physical activity (n = 311), the A allele of the FTO polymorphism was not associated with higher BMI (+0.17 per risk allele; 95% CI, −0.31 to 0.66; P = .48), body fat percentage (+0.40% per risk allele; 95% CI, −0.92 to 1.73; P = .56), or waist circumference (+0.60 cm per risk allele; 95% CI, −0.63 to 1.82; P = .34) after adjusting for center, sex, and age (Figure 2).

Place holder to copy figure label and caption
Figure 2.

Interaction effect between the FTO polymorphism rs9939609 and levels of moderate to vigorous physical activity (MVPA) (<60 min/d vs ≥60 min/d) on mean body mass index (calculated as weight in kilograms divided by height in meters squared), body fat percentage, and waist circumference. Error bars indicate 95% confidence intervals. Values are adjusted for center, sex, and age.

Graphic Jump Location

The results were similar in boys and girls and were similar when we adjusted for pubertal status instead of age (data not shown). Likewise, the results did not change after further adjusting for height squared in those models where waist circumference was involved (data not shown).

As expected, the minor A allele of rs9939609 was associated with higher levels of BMI, body fat percentage, and waist circumference in our adolescent population. We observed a gene × physical activity interaction for all of the study's body fat estimates, and the stratified analyses (<60 and ≥60 min/d of moderate to vigorous physical activity) revealed that the minor A allele was not associated with BMI, body fat percentage, or waist circumference in those adolescents who spent at least 60 min/d participating in moderate to vigorous physical activity. These findings have important public health implications and indicate that meeting the physical activity recommendations may offset the genetic predisposition to obesity associated with the FTO polymorphism in adolescents.

The results of this study are consistent with the findings of previous studies showing an association between FTO polymorphisms and obesity-related traits in different ethnic populations in adults, adolescents, or children.510 Further, we confirm that the association between the FTO rs9939609 polymorphism and adiposity estimates was attenuated once we took into account the levels of physical activity assessed by accelerometry.

To our knowledge, our study is the first to report an interaction between the FTO rs9939609 polymorphism and physical activity level on adiposity indices using objectively assessed physical activity in adolescents. Indeed, this study replicates previous findings of gene × physical activity interaction in adults.1113 Vimaleswaran et al11 reported an interaction between the FTO rs1121980 polymorphism and self-reported physical activity on BMI (P = .004) and waist circumference (P = .02) in 20 374 adults from the European Prospective Investigation Into Cancer and Nutrition–Norfolk Study. They showed a reduced but still significant (P < .001) effect of the FTO rs1121980 polymorphism on both BMI (+0.25 per risk allele) and waist circumference (+0.64 cm per risk allele) in physically active individuals compared with the inactive group (BMI, +0.44 per risk allele; waist circumference, +1.04 cm per risk allele). A similar effect size was observed in the Inter99 study composed of 5554 middle-aged Danish individuals.12 Andreasen et al12 also found an interaction between the FTO rs9939609 polymorphism and self-reported physical activity (for interaction, P = .007). Rampersaud et al13 observed an interaction between the FTO rs1861868 polymorphism and objectively assessed physical activity (for interaction, P = .01) in 704 Old Order Amish individuals. They reported that the increase per risk allele in BMI was attenuated in individuals in the upper half of the physical activity distribution (+0.30 per risk allele) compared with individuals within the lower half of the physical activity distribution (+1.12 per risk allele). Despite participants' differences in age and ethnicity, the effect sizes observed in our study are similar to those reported previously.

Our findings do not concur, however, with other studies that failed to observe an interaction between the FTO polymorphism and physical activity.1416 For example, Hakanen et al16 found no interaction between the FTO rs9939609 polymorphism and leisure-time physical activity in 438 Finnish adolescents aged 15 years. It is worth noting that most of the earlier-mentioned studies1116 assessed physical activity by a self-reported questionnaire, whereas we assessed physical activity by an objective method (ie, accelerometry). It is known that the assessment of physical activity by questionnaire may have lower accuracy, especially in young people.27,28 In epidemiologic research, self-reported questionnaires are common tools to assess physical activity level because they are easy to use and inexpensive. However, the sporadic nature of youths' physical activity makes these activities difficult to recall, quantify, and categorize. Also, youths have a lesser ability to accurately recall intensity, frequency, and especially duration of the activities.27

Findings from our study should be taken with caution owing to its cross-sectional nature. Lifestyle intervention studies in adolescents are needed to determine to what extent the effect of FTO on obesity-related traits can be modified, especially in genetically predisposed individuals. Findings from lifestyle intervention studies in adults are promising. Franks et al29 reported that the genetic (FTO rs9939609 polymorphism) effect on subcutaneous adipose tissue gain tended to be attenuated (P = .05) after a 1-year program of intensive lifestyle intervention.

In conclusion, our results suggest that physical activity can ameliorate the deleterious effect of the FTO rs9939609 polymorphism on body fat estimates in adolescents. Indeed, adolescents meeting the daily physical activity recommendations may overcome the effect of this gene on obesity-related traits.

Correspondence: Jonatan R. Ruiz, PhD, Unit for Preventive Nutrition, Department of Biosciences and Nutrition at NOVUM, Karolinska Institutet, Hälsovägen 7-9, SE-141 57 Huddinge, Sweden (ruizj@ugr.es).

Accepted for Publication: November 17, 2009.

Author Contributions: Dr Ruiz had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Ruiz, Dallongeville, Gottrand, De Henauw, and Sjöström. Acquisition of data: Ruiz, Ciarapica, Gottrand, Molnár, and Sjöström. Analysis and interpretation of data: Ruiz, Labayen, Ortega, Legry, Moreno, Dallongeville, Martínez-Gómez, Bokor, Manios, Sjöström, and Meirhaeghe. Drafting of the manuscript: Ruiz, Ciarapica, Sjöström, and Meirhaeghe. Critical revision of the manuscript for important intellectual content: Ruiz, Labayen, Ortega, Legry, Moreno, Dallongeville, Martínez-Gómez, Bokor, Manios, Gottrand, De Henauw, Molnár, and Sjöström. Statistical analysis: Ruiz, Legry, Dallongeville, and Meirhaeghe. Obtained funding: Ruiz, Moreno, Dallongeville, De Henauw, and Sjöström. Administrative, technical, and material support: Labayen, Ortega, Moreno, Gottrand, De Henauw, and Sjöström. Study supervision: Ruiz, Dallongeville, Molnár, Sjöström, and Meirhaeghe.

Financial Disclosure: None reported.

Funding/Support: The HELENA Study is supported by contract FOOD-CT-2005-007034 from the European Community Sixth RTD Framework Programme. This study is also supported by grants EX-2007-1124, EX-2008-0641, and AP2006-02464 from the Spanish Ministry of Education, grant RD08/0072 from the Maternal, Child Health, and Development Network of the Spanish Ministry of Health, the Swedish Council for Working Life and Social Research, and the ALPHA study (a European Union–funded study in the framework of the Public Health Programme [reference number 2006120]).

Disclaimer: The content of this article reflects only the authors' views. The additional HELENA Study Group members are not responsible for the content, and the European Community is not liable for any use that may be made of the information contained herein.

Box Section Ref ID

HELENA Study Group Members

Coordinator

Luis A. Moreno.

Core Group Members

Luis A. Moreno, Frederic Gottrand, Stefaan De Henauw, Marcela González-Gross, Chantal Gilbert.

Steering Committee

Anthony Kafatos (president), Luis A. Moreno, Christian Libersa, Stefaan De Henauw, Jackie Sánchez, Frederic Gottrand, Mathilde Kersting, Michael Sjöström, Denes Molnár, Marcela González-Gross, Jean Dallongeville, Chantal Gilbert, Gunnar Hall, Lea Maes, Luca Scalfi.

Project Manager

Pilar Meléndez.

Group Members

Luis A. Moreno, Jesús Fleta, José A. Casajús, Gerardo Rodríguez, Concepción Tomás, María I. Mesana, Germán Vicente-Rodríguez, Adoración Villarroya, Carlos M. Gil, Ignacio Ara, Juan Revenga, Carmen Lachen, Juan Fernández Alvira, Gloria Bueno, Aurora Lázaro, Olga Bueno, Juan F. León, Jesús M. Garagorri, Manuel Bueno, Juan Pablo Rey López, Iris Iglesia, Paula Velasco, Silvia Bel, Universidad de Zaragoza, Zaragoza, Spain; Ascensión Marcos, Julia Wärnberg, Esther Nova, Sonia Gómez, Esperanza Ligia Díaz, Javier Romeo, Ana Veses, Mari Angeles Puertollano, Belén Zapatera, Tamara Pozo, Consejo Superior de Investigaciones Científicas, Madrid, Spain; Laurent Béghin, Christian Libersa, Frederic Gottrand, Catalina Iliescu, Juliana Von Berlepsch, Université de Lille 2, Lille, France; Mathilde Kersting, Wolfgang Sichert-Hellert, Ellen Koeppen, Research Institute of Child Nutrition Dortmund, Rheinische Friedrich-Wilhelms-Universität Bonn, Dortmund, Germany; Denes Molnár, Eva Erhardt, Katalin Csernus, Katalin Török, Szilvia Bokor, Angela Angster, Enikö Nagy, Orsolya Kovács, Judit Repásy, Pécsi Tudományegyetem, University of Pécs, Pécs, Hungary; Anthony Kafatos, Caroline Codrington, María Plada, Angeliki Papadaki, Katerina Sarri, Anna Viskadourou, Christos Hatzis, Michael Kiriakakis, George Tsibinos, Constantine Vardavas Manolis Sbokos, Eva Protoyeraki, Maria Fasoulaki, University of Crete School of Medicine, Crete, Greece; Peter Stehle, Klaus Pietrzik, Marcela González-Gross, Christina Breidenassel, Andre Spinneker, Jasmin Al-Tahan, Miriam Segoviano, Anke Berchtold, Christine Bierschbach, Erika Blatzheim, Adelheid Schuch, Petra Pickert, Institut für Ernährungs und Lebensmittelwissenschaften–Ernährungphysiologie, Rheinische Friedrich-Wilhelms-Universität, Dortmund, Germany; Manuel J. Castillo, Ángel Gutiérrez, Francisco B. Ortega, Jonatan R. Ruiz, Enrique G. Artero, Vanesa España-Romero, David Jiménez-Pavón, Palma Chillón, University of Granada, Granada, Spain; Davide Arcella, Giovina Catasta, Laura Censi, Donatella Ciarapica, Marika Ferrari, Cinzia Le Donne, Catherine Leclerq, Luciana Magrì, Giuseppe Maiani, Rafaela Piccinelli, Angela Polito, Raffaela Spada, Elisabetta Toti, Istituto Nazionalen di Ricerca per gli Alimenti e la Nutrizione, Roma, Italy; Luca Scalfi, Paola Vitaglione, Concetta Montagnese, Department of Food Science, University of Napoli Federico II, Napoli, Italy; Ilse De Bourdeaudhuij, Stefaan De Henauw, Tineke De Vriendt, Lea Maes, Christophe Matthys, Carine Vereecken, Mieke de Maeyer, Charlene Ottevaere, Ghent University, Ghent, Belgium; Kurt Widhalm, Katharina Phillipp, Sabine Dietrich, Birgit Kubelka, Marion Boriss-Riedl, Medical University of Vienna, Vienna, Austria; Yannis Manios, Eva Grammatikaki, Zoi Bouloubasi, Tina Louisa Cook, Sofia Eleutheriou, Orsalia Consta, George Moschonis, Ioanna Katsaroli, George Kraniou, Stalo Papoutsou, Despoina Keke, Ioanna Petraki, Elena Bellou, Sofia Tanagra, Kostalenia Kallianoti, Dionysia Argyropoulou, Katerina Kondaki, Stamatoula Tsikrika, Christos Karaiskos, Harokopio University, Athens, Greece; Jean Dallongeville, Aline Meirhaeghe, Institut Pasteur de Lille, Lille, France; Michael Sjöström, Patrick Bergman, María Hagströmer, Lena Hallström, Mårten Hallberg, Eric Poortvliet, Julia Wärnberg, Nico Rizzo, Linda Beckman, Anita Hurtig Wennlöf, Emma Patterson, Lydia Kwak, Lars Cernerud, Per Tillgren, Stefaan Sörensen, Karolinska Institutet, Huddinge, Sweden; Jackie Sánchez-Molero, Elena Picó, Maite Navarro, Blanca Viadel, José Enrique Carreres, Gema Merino, Rosa Sanjuán, María Lorente, María José Sánchez, Sara Castelló, Asociación de Investigación de la Industria Agroalimentaria, Valencia, Spain; Chantal Gilbert, Sarah Thomas, Elaine Allchurch, Peter Burguess, Campden and Chorleywood Food Research Association, Gloucestershire, England; Gunnar Hall, Annika Astrom, Anna Sverkén, Agneta Broberg, SIK–Institutet för Livsmedel och Bioteknik, Gothenburg, Sweden; Annick Masson, Claire Lehoux, Pascal Brabant, Philippe Pate, Laurence Fontaine, Meurice Recherche and Development asbl, Brussels, Belgium; Andras Sebok, Tunde Kuti, Adrienn Hegyi, Campden and Chorleywood Food Development Institute, Budapest, Hungary; Cristina Maldonado, Ana Llorente, Productos Aditivos SA, Montcada i Reixac, Spain; Emilio García, Cárnicas Serrano SL, Valencia, Spain; Holger von Fircks, Marianne Lilja Hallberg, Maria Messerer, Cederroth International AB, Upplands Väsby, Sweden; Mats Larsson, Helena Fredriksson, Viola Adamsson, Ingmar Börjesson, Lantmännen Food R&D, Stockholm, Sweden; Laura Fernández, Laura Smillie, Josephine Wills, European Food Information Council, Brussels, Belgium; Marcela González-Gross, Agustín Meléndez, Pedro J. Benito, Javier Calderón, David Jiménez-Pavón, Jara Valtueña, Paloma Navarro, Alejandro Urzanqui, Ulrike Albers, Raquel Pedrero, Juan José Gómez Lorente, Universidad Politécnica de Madrid, Madrid, Spain.

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Jonsson  ARenstrom  FLyssenko  V  et al.  Assessing the effect of interaction between an FTO variant (rs9939609) and physical activity on obesity in 15 925 Swedish and 2511 Finnish adults. Diabetologia 2009;52 (7) 1334- 1338
PubMed
Hakanen  MRaitakari  OTLehtimaki  T  et al.  FTO genotype is associated with body mass index after the age of seven years but not with energy intake or leisure-time physical activity. J Clin Endocrinol Metab 2009;94 (4) 1281- 1287
PubMed
US Department of Health and Human Services, 2008 Physical activity guidelines for Americans. http://www.health.gov/PAGuidelines/. Accessed July 6, 2009
Moreno  LADe Henauw  SGonzález-Gross  M  et al. HELENA Study Group, Design and implementation of the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study. Int J Obes (Lond) 2008;32 ((suppl 5)) S4- S11
PubMed
Moreno  LAGonzález-Gross  MKersting  M  et al. HELENA Study Group, Assessing, understanding and modifying nutritional status, eating habits and physical activity in European adolescents: the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Study. Public Health Nutr 2008;11 (3) 288- 299
PubMed
Béghin  LCastera  MManios  Y  et al. HELENA Study Group, Quality assurance of ethical issues and regulatory aspects relating to good clinical practices in the HELENA Cross-Sectional Study. Int J Obes (Lond) 2008;32 ((suppl 5)) S12- S18
PubMed
Nagy  EVicente-Rodriguez  GManios  Y  et al. HELENA Study Group, Harmonization process and reliability assessment of anthropometric measurements in a multicenter study in adolescents. Int J Obes (Lond) 2008;32 ((suppl 5)) S58- S65
PubMed
Slaughter  MHLohman  TGBoileau  RA  et al.  Skinfold equations for estimation of body fatness in children and youth. Hum Biol 1988;60 (5) 709- 723
PubMed
Tanner  JMWhitehouse  RH Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child 1976;51 (3) 170- 179
PubMed
Iliescu  CBéghin  LMaes  L  et al. HELENA Study Group, Socioeconomic questionnaire and clinical assessment in the HELENA Cross-Sectional Study: methodology. Int J Obes (Lond) 2008;32 ((suppl 5)) S19- S25
PubMed
Ward  DSEvenson  KRVaughn  ARodgers  ABTroiano  RP Accelerometer use in physical activity: best practices and research recommendations. Med Sci Sports Exerc 2005;37 (11) ((suppl)) S582- S588
PubMed
Strong  WBMalina  RMBlimkie  CJ  et al.  Evidence based physical activity for school-age youth. J Pediatr 2005;146 (6) 732- 737
PubMed
Ruiz  JROrtega  FB Physical activity and cardiovascular disease risk factors in children and adolescents. Curr Cardiovasc Risk Rep 2009;3 (4) 281- 28710.1007/s12170-009-0043-6
Hagströmer  MBergman  PDe Bourdeaudhuij  I  et al. HELENA Study Group, Concurrent validity of a modified version of the International Physical Activity Questionnaire (IPAQ-A) in European adolescents: the HELENA Study. Int J Obes (Lond) 2008;32 ((suppl 5)) S42- S48
PubMed
Franks  PWJablonski  KADelahanty  LM  et al. Diabetes Prevention Program Research Group, Assessing gene-treatment interactions at the FTO and INSIG2 loci on obesity-related traits in the Diabetes Prevention Program. Diabetologia 2008;51 (12) 2214- 2223
PubMed

Figures

Place holder to copy figure label and caption
Figure 1.

Association between the FTO polymorphism rs9939609 and mean body mass index (calculated as weight in kilograms divided by height in meters squared), body fat percentage, and waist circumference. Error bars indicate 95% confidence intervals. Values are adjusted for center, sex, and age.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Interaction effect between the FTO polymorphism rs9939609 and levels of moderate to vigorous physical activity (MVPA) (<60 min/d vs ≥60 min/d) on mean body mass index (calculated as weight in kilograms divided by height in meters squared), body fat percentage, and waist circumference. Error bars indicate 95% confidence intervals. Values are adjusted for center, sex, and age.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable. Characteristics of the Study Cohort

References

Willer  CJSpeliotes  EKLoos  RJ  et al. Wellcome Trust Case Control Consortium; Genetic Investigation of Anthropometric Traits Consortium, Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 2009;41 (1) 25- 34
PubMed
Thorleifsson  GWalters  GBGudbjartsson  DF  et al.  Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet 2009;41 (1) 18- 24
PubMed
Marti  AMartinez-González  MAMartinez  JA Interaction between genes and lifestyle factors on obesity. Proc Nutr Soc 2008;67 (1) 1- 8
PubMed
Loos  RJRankinen  T Gene-diet interactions on body weight changes. J Am Diet Assoc 2005;105 (5) ((suppl 1)) S29- S34
PubMed
Cecil  JETavendale  RWatt  PHetherington  MMPalmer  CN An obesity-associated FTO gene variant and increased energy intake in children. N Engl J Med 2008;359 (24) 2558- 2566
PubMed
Frayling  TMTimpson  NJWeedon  MN  et al.  A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007;316 (5826) 889- 894
PubMed
Scuteri  ASanna  SChen  WM  et al.  Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 2007;3 (7) e115
PubMed10.1371/journal.pgen.0030115
Hinney  ANguyen  TTScherag  A  et al.  Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants. PLoS One 2007;2 (12) e1361
PubMed10.1371/journal.pone.0001361
Dina  CMeyre  DGallina  S  et al.  Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet 2007;39 (6) 724- 726
PubMed
Legry  VCottel  DFerrieres  J  et al.  Effect of an FTO polymorphism on fat mass, obesity, and type 2 diabetes mellitus in the French MONICA Study. Metabolism 2009;58 (7) 971- 975
PubMed
Vimaleswaran  KSLi  SZhao  JH  et al.  Physical activity attenuates the body mass index-increasing influence of genetic variation in the FTO gene. Am J Clin Nutr 2009;90 (2) 425- 428
PubMed
Andreasen  CHStender-Petersen  KLMogensen  MS  et al.  Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes 2008;57 (1) 95- 101
PubMed
Rampersaud  EMitchell  BDPollin  TI  et al.  Physical activity and the association of common FTO gene variants with body mass index and obesity. Arch Intern Med 2008;168 (16) 1791- 1797
PubMed
Cornes  BKLind  PAMedland  SEMontgomery  GWNyholt  DRMartin  NG Replication of the association of common rs9939609 variant of FTO with increased BMI in an Australian adult twin population but no evidence for gene by environment (G × E) interaction. Int J Obes (Lond) 2009;33 (1) 75- 79
PubMed
Jonsson  ARenstrom  FLyssenko  V  et al.  Assessing the effect of interaction between an FTO variant (rs9939609) and physical activity on obesity in 15 925 Swedish and 2511 Finnish adults. Diabetologia 2009;52 (7) 1334- 1338
PubMed
Hakanen  MRaitakari  OTLehtimaki  T  et al.  FTO genotype is associated with body mass index after the age of seven years but not with energy intake or leisure-time physical activity. J Clin Endocrinol Metab 2009;94 (4) 1281- 1287
PubMed
US Department of Health and Human Services, 2008 Physical activity guidelines for Americans. http://www.health.gov/PAGuidelines/. Accessed July 6, 2009
Moreno  LADe Henauw  SGonzález-Gross  M  et al. HELENA Study Group, Design and implementation of the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study. Int J Obes (Lond) 2008;32 ((suppl 5)) S4- S11
PubMed
Moreno  LAGonzález-Gross  MKersting  M  et al. HELENA Study Group, Assessing, understanding and modifying nutritional status, eating habits and physical activity in European adolescents: the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Study. Public Health Nutr 2008;11 (3) 288- 299
PubMed
Béghin  LCastera  MManios  Y  et al. HELENA Study Group, Quality assurance of ethical issues and regulatory aspects relating to good clinical practices in the HELENA Cross-Sectional Study. Int J Obes (Lond) 2008;32 ((suppl 5)) S12- S18
PubMed
Nagy  EVicente-Rodriguez  GManios  Y  et al. HELENA Study Group, Harmonization process and reliability assessment of anthropometric measurements in a multicenter study in adolescents. Int J Obes (Lond) 2008;32 ((suppl 5)) S58- S65
PubMed
Slaughter  MHLohman  TGBoileau  RA  et al.  Skinfold equations for estimation of body fatness in children and youth. Hum Biol 1988;60 (5) 709- 723
PubMed
Tanner  JMWhitehouse  RH Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child 1976;51 (3) 170- 179
PubMed
Iliescu  CBéghin  LMaes  L  et al. HELENA Study Group, Socioeconomic questionnaire and clinical assessment in the HELENA Cross-Sectional Study: methodology. Int J Obes (Lond) 2008;32 ((suppl 5)) S19- S25
PubMed
Ward  DSEvenson  KRVaughn  ARodgers  ABTroiano  RP Accelerometer use in physical activity: best practices and research recommendations. Med Sci Sports Exerc 2005;37 (11) ((suppl)) S582- S588
PubMed
Strong  WBMalina  RMBlimkie  CJ  et al.  Evidence based physical activity for school-age youth. J Pediatr 2005;146 (6) 732- 737
PubMed
Ruiz  JROrtega  FB Physical activity and cardiovascular disease risk factors in children and adolescents. Curr Cardiovasc Risk Rep 2009;3 (4) 281- 28710.1007/s12170-009-0043-6
Hagströmer  MBergman  PDe Bourdeaudhuij  I  et al. HELENA Study Group, Concurrent validity of a modified version of the International Physical Activity Questionnaire (IPAQ-A) in European adolescents: the HELENA Study. Int J Obes (Lond) 2008;32 ((suppl 5)) S42- S48
PubMed
Franks  PWJablonski  KADelahanty  LM  et al. Diabetes Prevention Program Research Group, Assessing gene-treatment interactions at the FTO and INSIG2 loci on obesity-related traits in the Diabetes Prevention Program. Diabetologia 2008;51 (12) 2214- 2223
PubMed

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