title: Interaction between GPR120 p.R270H loss-of-function variant and dietary fat intake on incident type 2 diabetes risk in the D.E.S.I.R. study.
abstract: GPR120 (encoded by FFAR4) is a lipid sensor that plays an important role in the control of energy balance. GPR120 is activated by long chain fatty acids (FAs) including omega-3 FAs. In humans, the loss of function p.R270H variant of the gene FFAR4 has been associated with a lower protein activity, an increased risk of obesity and higher fasting plasma glucose levels. The aim of this study was to investigate whether p.R270H interacts with dietary fat intake to modulate the risk of type 2 diabetes (T2D, 198 incident; 368 prevalent cases) and overweight (787 incident and 2891 prevalent cases) in the prospective D.E.S.I.R. study (n = 5,212, 9 years follow-up).
  
  
  
  The association of p.R270H with dietary fat and total calories was assessed by linear mixed models. The interaction between p.R270H and dietary fat on T2D and overweight was assessed by logistic regression analysis. The p.R270H variant had a minor allele frequency of 1.45% and was not significantly associated with total calories intake, fat intake or the total calories derived from fat (%). However, there was a significant interaction between p.R270H and dietary fat modulating the incidence of T2D (Pinteraction = 0.02) where the H-carriers had a higher risk of T2D than RR homozygotes in the low fat intake category only. The interaction between p.R270H and fat intake modulating the incidence and prevalence of overweight was not significant.
  
  
  
  The p.R270H variant of GPR120 modulates the risk of T2D in interaction with dietary fat intake in the D.E.S.I.R.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches des Cordeliers, Research Unit 1138, Paris, France; Paris Diderot University, Sorbonne Paris Cité, Paris, France; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Lamri
authors.affiliation: CNRS-UMR8199, Lille Pasteur Institute, Lille, France; Lille University, Lille, France; European Genomic Institute for Diabetes (EGID), FR 3508, Lille, France.
authors.forename: A
authors.initials: A
authors.lastname: Bonnefond
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Meyre
authors.affiliation: INSERM, CESP Centre for Research in Epidemiology and Population Health, U1018, Villejuif, France; Universities of St Quentin-Versailles and Paris Sud 11, UMRS 1018, Villejuif, France.
authors.forename: B
authors.initials: B
authors.lastname: Balkau
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches des Cordeliers, Research Unit 1138, Paris, France; Paris Diderot University, Sorbonne Paris Cité, Paris, France; Assistance Publique Hôpitaux de Paris (APHP), Bichat Hospital, Department of Diabetology, Endocrinology and Nutrition, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Roussel
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches des Cordeliers, Research Unit 1138, Paris, France; Paris Diderot University, Sorbonne Paris Cité, Paris, France; Assistance Publique Hôpitaux de Paris (APHP), Bichat Hospital, Department of Diabetology, Endocrinology and Nutrition, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Marre
authors.affiliation: CNRS-UMR8199, Lille Pasteur Institute, Lille, France; Lille University, Lille, France; European Genomic Institute for Diabetes (EGID), FR 3508, Lille, France.
authors.forename: P
authors.initials: P
authors.lastname: Froguel
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches des Cordeliers, Research Unit 1138, Paris, France; Paris Diderot University, Sorbonne Paris Cité, Paris, France. Electronic address: frederic.fumeron@inserm.fr.
authors.forename: F
authors.initials: F
authors.lastname: Fumeron
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D004041:Dietary Fats / Q000009:adverse effects*; D002149:Energy Intake; D005260:Female; D005602:France / Q000453:epidemiology; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015994:Incidence; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000453:epidemiology / Q000235:genetics; D010641:Phenotype; D015995:Prevalence; D011446:Prospective Studies; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012307:Risk Factors; D013997:Time Factors
chemical_list: D004041:Dietary Fats; C519853:FFAR4 protein, human; D043562:Receptors, G-Protein-Coupled
keywords: Dietary fat intake; Free fatty acid receptor 4 (FFAR4); G-protein coupled receptor 120 (GPR120); Gene × diet interaction; Longitudinal; Overweight; Type 2 diabetes (T2D)