A Lamri1, A Bonnefond2, D Meyre3, B Balkau4, R Roussel5, M Marre5, P Froguel2, F Fumeron6. 1. 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. 2. CNRS-UMR8199, Lille Pasteur Institute, Lille, France; Lille University, Lille, France; European Genomic Institute for Diabetes (EGID), FR 3508, Lille, France. 3. Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada. 4. 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. 5. 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. 6. 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.
Abstract
BACKGROUND AND AIMS: 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). METHODS AND RESULTS: 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. CONCLUSION: The p.R270H variant of GPR120 modulates the risk of T2D in interaction with dietary fat intake in the D.E.S.I.R.
BACKGROUND AND AIMS: 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). METHODS AND RESULTS: 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. CONCLUSION: The p.R270H variant of GPR120 modulates the risk of T2D in interaction with dietary fat intake in the D.E.S.I.R.