Identifier to cite or link to this item: http://hdl.handle.net/20.500.13003/12977
Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to the Mediterranean diet pattern is low
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eISSN: 1475-2840
WOS ID: 000311210400001
Scopus EID: 2-s2.0-84868288658
PMID: 23130628
Embase PUI: L52293348
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Ortega-Azorin, Carolina; Sorli, Jose V.; Asensio, Eva M.; Coltell, Oscar; Angel Martinez-Gonzalez, Miguel; Salas-Salvado, Jordi; Covas, Maria-Isabel; Aros, Fernando; Lapetra, Jose; Serra-Majem, Lluis; Gomez-Gracia, Enrique; Fiol Sala, Miquel

Publication date
2012-11-06Document type
research articleCitation
Ortega-Azorin C, Sorli JV, Asensio EM, Coltell O, Martinez-Gonzalez MA, Salas-Salvado J, et al. Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to the Mediterranean diet pattern is low. Cardiovasc Diabetol. 2012 Nov 06;11:137.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.
Publisher version
https://dx.doi.org/10.1186/1475-2840-11-137MeSH
Aged, 80 and overAged
Fasting
Humans
Receptor, Melanocortin, Type 4
Phenotype
Male
Multivariate Analysis
Chi-Square Distribution
Patient Compliance
Female
Body Mass Index
Nutrigenomics
Polymorphism, Genetic
Surveys and Questionnaires
Diabetes Mellitus, Type 2
Genetic Predisposition to Disease
Blood Glucose
Case-Control Studies
Spain
Gene Frequency
Middle Aged
Nutritional Status
Proteins
Diet, Mediterranean
Odds Ratio
Gene-Environment Interaction
Alpha-Ketoglutarate-Dependent Dioxygenase FTO
Linear Models
Logistic Models
DeCS
Modelos LinealesDieta Mediterránea
Receptor de Melanocortina Tipo 4
Modelos Logísticos
Oportunidad Relativa
Femenino
Masculino
Proteínas
Interacción Gen-Ambiente
Persona de Mediana Edad
Glucemia
Frecuencia de los Genes
Diabetes Mellitus Tipo 2
Índice de Masa Corporal
Distribución de Chi-Cuadrado
Predisposición Genética a la Enfermedad
Análisis Multivariante
Estado Nutricional
Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato
Cooperación del Paciente
Nutrigenómica
Humanos
Ayuno
Anciano
Fenotipo
Anciano de 80 o más Años
Encuestas y Cuestionarios
Polimorfismo Genético
España
Estudios de Casos y Controles