Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-11-06

AUTHORS

Carolina Ortega-Azorín, Jose V Sorlí, Eva M Asensio, Oscar Coltell, Miguel Ángel Martínez-González, Jordi Salas-Salvadó, Maria-Isabel Covas, Fernando Arós, José Lapetra, Lluís Serra-Majem, Enrique Gómez-Gracia, Miquel Fiol, Guillermo Sáez-Tormo, Xavier Pintó, Miguel Angel Muñoz, Emilio Ros, Jose M Ordovás, Ramon Estruch, Dolores Corella

ABSTRACT

BACKGROUND: Although the fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) genes have been consistently associated with obesity risk, the association between the obesity-risk alleles with type 2 diabetes is still controversial. In some recent meta-analyses in which significant results have been reported, the associations disappeared after adjustment for body mass index (BMI). However gene-diet interactions with dietary patterns have not been investigated. Our main aim was to analyze whether these associations are modulated by the level of adherence to the Mediterranean Diet (MedDiet). METHODS: Case-control study in 7,052 high cardiovascular risk subjects (3,430 type 2 diabetes cases and 3,622 non-diabetic subjects) with no differences in BMI. Diet was assessed by validated questionnaires. FTO-rs9939609 and MC4R-rs17782313 were determined. An aggregate genetic score was calculated to test additive effects. Gene-diet interactions were analyzed. RESULTS: Neither of the polymorphisms was associated with type 2 diabetes in the whole population. However, we found consistent gene-diet interactions with adherence to the MedDiet both for the FTO-rs9939609 (P-interaction=0.039), the MC4R-rs17782313 (P-interaction=0.009) and for their aggregate score (P-interaction=0.006). When adherence to the MedDiet was low, carriers of the variant alleles had higher type 2 diabetes risk (OR=1.21, 95%CI: 1.03-1.40; P=0.019 for FTO-rs9939609 and OR=1.17, 95%CI:1.01-1.36; P=0.035 for MC4R-rs17782313) than wild-type subjects. However, when adherence to the MedDiet was high, these associations disappeared (OR=0.97, 95%CI: 0.85-1.16; P=0.673 for FTO-rs9939609 and OR=0.89, 95%CI:0.78-1.02; P=0.097 for MC4R-rs17782313). These gene-diet interactions remained significant even after adjustment for BMI. As MedDiet is rich in folate, we also specifically examined folate intake and detected statistically significant interaction effects on fasting plasma glucose concentrations in non-diabetic subjects. However these findings should be interpreted with caution because folate intake may simply reflect a healthy dietary pattern. CONCLUSIONS: These novel results suggest that the association of the FTO-rs9939609 and the MC4R-rs17782313 polymorphisms with type 2 diabetes depends on diet and that a high adherence to the MedDiet counteracts the genetic predisposition. More... »

PAGES

137-137

References to SciGraph publications

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  • Journal

    TITLE

    Cardiovascular Diabetology

    ISSUE

    1

    VOLUME

    11

    Author Affiliations

  • CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
  • Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA
  • Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, Pamplona, Spain
  • Human Nutrition Unit, Faculty of Medicine, IISPV, University Rovira i Virgili, Reus, Spain
  • Cardiovascular Epidemiology Unit, Municipal Institut for Medical Research (IMIM), Barcelona, Spain
  • Department of Cardiology, Hospital Txagorritxu, Vitoria, Spain
  • Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain
  • Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain
  • Department of Epidemiology, School of Medicine, University of Malaga, Málaga, Spain
  • University Institute for Health Sciences Investigation, Hospital Son Dureta, Palma de Mallorca, Spain
  • Department of Biochemistry, School of Medicine, University of Valencia, Valencia, Spain
  • Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain
  • Primary Care Division, Catalan Institute of Health, Barcelona, Spain
  • Lipid Clinic, Endocrinology and Nutrition Service, Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clinic, Barcelona, Spain
  • IMDEA Alimentación, Madrid, Spain
  • Department of Internal Medicine, Hospital Clinic, IDIBAPS, Barcelona, Spain
  • Genetic and Molecular Epidemiology Unit, Valencia University, Blasco Ibañez, 15, 46010, Valencia, Spain
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/1475-2840-11-137

    DOI

    http://dx.doi.org/10.1186/1475-2840-11-137

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1031123255

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23130628


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    505 Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, Valencia, Spain
    506 Genetic and Molecular Epidemiology Unit, Valencia University, Blasco Ibañez, 15, 46010, Valencia, Spain
    507 Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA
    508 rdf:type schema:Organization
    509 grid-institutes:grid.5924.a schema:alternateName Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, Pamplona, Spain
    510 schema:name Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, Pamplona, Spain
    511 rdf:type schema:Organization
     




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