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Interaction of Dietary and Genetic Factors Influencing Body Iron Status and Risk of Type 2 Diabetes Within the EPIC-InterAct Study.

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Meidtner, Karina 
Kröger, Janine 
van der Schouw, Yvonne T 
Bendinelli, Benedetta 


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 [HFEH63D], rs1800562 [HFEC282Y], rs236918 [PCK7], rs744653 [SLC40A1], and rs855791 [TMPRSS6V736A]) 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.



Cohort Studies, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Diet, Europe, Female, Ferritins, Gene-Environment Interaction, Genome-Wide Association Study, Hemochromatosis Protein, Humans, Iron, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Transferrin

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Diabetes Care

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American Diabetes Association
Medical Research Council (G1000143)
Cancer Research Uk (None)
Cancer Research Uk (None)
Cancer Research Uk (None)
Medical Research Council (G0401527)
Cancer Research Uk (None)
Department of Health (via National Institute for Health Research (NIHR)) (unknown)
National Institute for Health Research (NIHR) (NF-SI-0512-10114)
Medical Research Council (MC_UU_12015/1)
Medical Research Council (MC_UU_12015/5)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
Wellcome Trust (097451/Z/11/Z)
Medical Research Council (MR/N003284/1)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
European Commission (602068)
Medical Research Council (G0401527/1)
Multiple funders acknowledged on paper.