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Open Access 01-12-2012 | Original investigation

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

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

Published in: Cardiovascular Diabetology | Issue 1/2012

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.

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Title: 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
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
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Cardiovascular Diabetology / Issue 1/2012
Electronic ISSN: 1475-2840
DOI: https://doi.org/10.1186/1475-2840-11-137

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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

Abstract

Background

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Conclusions

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At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page