Interaction of Dietary and Genetic Factors Influencing Body Iron Status and Risk of Type 2 Diabetes Within the EPIC-InterAct Study
Year: 2017
Type: article
Abstract: OBJECTIVE Meat intake has been consistently shown to be positively associated with incident type 2 diabetes. Part of that association may be mediated by body iron status, which is influenced by genetic factors. We aimed to test for interactions of genetic and dietary factors influencing body iron status in relation to the risk of incident type 2 diabetes. RESEARCH DESIGN AND METHODS The case-cohort comprised 9,347 case subjects and 12,301 subcohort participants from eight European countries. Single nucleotide polymorphisms (SNPs) were selected from genome-wide association studies on iron status biomarkers and candidate gene studies. A ferritin-related gene score was constructed. Multiplicative and additive interactions of heme iron and SNPs as well as the gene score were evaluated using Cox proportional hazards regression. RESULTS Higher heme iron intake (per 1 SD) was associated with higher ferritin levels (β = 0.113 [95% CI 0.082; 0.144]), but not with transferrin (−0.019 [−0.043; 0.006]) or transferrin saturation (0.016 [−0.006; 0.037]). Five SNPs located in four genes (rs1799945 [HFE H63D], rs1800562 [HFE C282Y], rs236918 [PCK7], rs744653 [SLC40A1], and rs855791 [TMPRSS6 V736A]) were associated with ferritin. We did not detect an interaction of heme iron and the gene score on the risk of diabetes in the overall study population (Padd = 0.16, Pmult = 0.21) but did detect a trend toward a negative interaction in men (Padd = 0.04, Pmult = 0.03). CONCLUSIONS We found no convincing evidence that the interplay of dietary and genetic factors related to body iron status associates with type 2 diabetes risk above the level expected from the sum or product of the two individual exposures.
Source: Diabetes Care
DOI: 10.2337/dc17-1080
Authors: Karina Meidtner, Clara Podmore, Janine Kröger, Yvonne T. van der Schouw, Benedetta Bendinelli, Claudia Agnoli, Larraitz Arriola, Aurelio Barricarte, Heiner Boeing, Amanda J. Cross, Courtney Dow, Kim Ekblom, Guy Fagherazzi, Paul W. Franks, Marc J. Gunter, José María Huerta, Paula Jakszyn, Mazda Jenab, Verena A. Katzke, Timothy J. Key, Kay Tee Khaw, Tilman Kühn, Cecilie Kyrø, Francesca Romana Mancini, Olle Melander, Peter M. Nilsson, Kim Overvad, Domenico Palli, Salvatore Panico, J. Ramón Quirós, Miguel Rodríguez-Barranco, Carlotta Sacerdote, Ivonne Sluijs, Magdalena Stepien, Anne Tjonneland, Rosario Tumino, Nita G. Forouhi, Stephen J. Sharp, Claudia Langenberg, Matthias B. Schulze, Elio Riboli, Nicholas J. Wareham
Institutions: German Center for Diabetes Research, German Institute of Human Nutrition, University of Cambridge, Medical Research Council, University Medical Center Utrecht, Istituto per lo Studio e la Prevenzione Oncologica, Fondazione IRCCS Istituto Nazionale dei Tumori, Basque Government, Centro de Investigación Biomédica en Red, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Navarre Institute of Health Research, Imperial College London, Université Paris-Sud, Inserm, Institut Gustave Roussy, Centre de recherche en Epidémiologie et Santé des Populations, Umeå University, Lund University, Centre international de recherche sur le cancer, Instituto Murciano de Investigación Biosanitaria, Institut Català d'Oncologia, Universitat Ramon Llull, German Cancer Research Center, University of Oxford, Danish Cancer Society, Aarhus University, Aalborg University Hospital, Federico II University Hospital, University of Naples Federico II, Gobierno del Principado de Asturias, Universidad de Granada, Instituto de Investigación Biosanitaria de Granada, Andalusian School of Public Health, Azienda Ospedaliera Citta' della Salute e della Scienza di Torino, Italian institute for Genomic Medicine, Piedmont Reference Center for Epidemiology and Cancer Prevention, University of Turin, Associazione Iblea per la Ricerca Epidemiologica E.T.S.
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: World Health Organization, Compagnia di San Paolo, Deutsches Krebsforschungszentrum, Wellcome Trust, Cancer Research UK, National Institute for Health and Care Research, European Commission, Bundesministerium für Bildung und Forschung, Generalitat de Catalunya, Cambridge University Hospitals, Universitair Medisch Centrum Utrecht, Hjärt-Lungfonden, Novo Nordisk, Vetenskapsrådet, Deutsche Krebshilfe, Novo Nordisk Fonden, Sixth Framework Programme, Medical Research Council, World Cancer Research Fund, Agència de Gestió d'Ajuts Universitaris i de Recerca, Agentschap NL
Awards: G1715861748, G219746026, G2826529823, Wellcome Trust PhD Programme for Clinicians at the University of Cambridge., G3803372573, G4990591557, G5384371102, G5897142711, G5976813381, NIHR Senior Investigator Award, G6594529311, G6723261869, G6957823285, Global initiative on gene-environment interaction on diabetes/obesity risk, NIHR Senior Investigator Award, G8585681489, NIHR Senior Investigator Award, G892496435
OpenAlex ID: W2770884347