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. 2018 Feb;41(2):277-285.
doi: 10.2337/dc17-1080. Epub 2017 Nov 22.

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

Karina Meidtner  1   2 , Clara Podmore  3 , Janine Kröger  1 , Yvonne T van der Schouw  4 , Benedetta Bendinelli  5 , Claudia Agnoli  6 , Larraitz Arriola  7   8   9 , Aurelio Barricarte  9   10   11 , Heiner Boeing  12 , Amanda J Cross  13 , Courtney Dow  14   15   16 , Kim Ekblom  17 , Guy Fagherazzi  14   15   16 , Paul W Franks  18   19 , Marc J Gunter  20 , José María Huerta  8   21 , Paula Jakszyn  22   23 , Mazda Jenab  20 , Verena A Katzke  24 , Timothy J Key  25 , Kay Tee Khaw  26 , Tilman Kühn  24 , Cecilie Kyrø  27 , Francesca Romana Mancini  14   15   16 , Olle Melander  18 , Peter M Nilsson  18 , Kim Overvad  28   29 , Domenico Palli  5 , Salvatore Panico  30 , J Ramón Quirós  31 , Miguel Rodríguez-Barranco  9   32 , Carlotta Sacerdote  33   34 , Ivonne Sluijs  4 , Magdalena Stepien  20 , Anne Tjonneland  27 , Rosario Tumino  35   36 , Nita G Forouhi  3 , Stephen J Sharp  3 , Claudia Langenberg  3 , Matthias B Schulze  37   2 , Elio Riboli  13 , Nicholas J Wareham  3
Affiliations

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

Karina Meidtner et al. Diabetes Care. 2018 Feb.

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.

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Conflict of interest statement

All authors declare that there are no conflicts of interest.

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