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  • 1. Meidtner, Karina
    et al.
    Podmore, Clara
    Kroger, Janine
    van der Schouw, Yvonne T.
    Bendinelli, Benedetta
    Agnoli, Claudia
    Arriola, Larraitz
    Barricarte, Aurelio
    Boeing, Heiner
    Cross, Amanda J.
    Dow, Courtney
    Ekblom, Kim
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Fagherazzi, Guy
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Gunter, Marc J.
    Huerta, Jose Maria
    Jakszyn, Paula
    Jenab, Mazda
    Katzke, Verena A.
    Key, Timothy J.
    Khaw, Kay Tee
    Kuhn, Tilman
    Kyro, Cecilie
    Mancini, Francesca Romana
    Melander, Olle
    Nilsson, Peter M.
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Quiros, J. Ramon
    Rodriguez-Barranco, Miguel
    Sacerdote, Carlotta
    Sluijs, Ivonne
    Stepien, Magdalena
    Tjonneland, Anne
    Tumino, Rosario
    Forouhi, Nita G.
    Sharp, Stephen J.
    Langenberg, Claudia
    Schulze, Matthias B.
    Riboli, Elio
    Wareham, Nicholas J.
    Interaction of Dietary and Genetic Factors Influencing Body Iron Status and Risk of Type 2 Diabetes Within the EPIC-InterAct Study2018In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 41, no 2, p. 277-285Article in journal (Refereed)
    Abstract [en]

    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 [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.

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