Interaction of dietary and genetic factors influencing body iron status and risk of type 2 diabetes within the EPIC-InterAct study

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

doi:10.2337/dc17-1080

Interaction of dietary and genetic factors influencing body iron status and risk of type 2 diabetes within the EPIC-InterAct study

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. KeyKay 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

Facultat de Ciències de la Salut Blanquerna

Producció científica: Article en revista indexada › Article › Avaluat per experts

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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 (b = 0.113 [95% CI 0.082; 0.144]), but not with transferrin (20.019 [20.043; 0.006]) or transferrin saturation (0.016 [20.006; 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 (P_add = 0.16, P_mult = 0.21) but did detect a trend toward a negative interaction in men (P_add = 0.04, P_mult = 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.

Idioma original	Anglès
Pàgines (de-a)	277-285
Nombre de pàgines	9
Revista	Diabetes Care
Volum	41
Número	2
DOIs	https://doi.org/10.2337/dc17-1080
Estat de la publicació	Publicada - 1 de febr. 2018

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10.2337/dc17-1080

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Meidtner, K., Podmore, C., Kröger, J., Van Der Schouw, Y. T., Bendinelli, B., Agnoli, C., Arriola, L., Barricarte, A., Boeing, H., Cross, A. J., Dow, C., Ekblom, K., Fagherazzi, G., Franks, P. W., Gunter, M. J., Huerta, J. M., Jakszyn, P., Jenab, M., Katzke, V. A., ... Wareham, N. J. (2018). Interaction of dietary and genetic factors influencing body iron status and risk of type 2 diabetes within the EPIC-InterAct study. Diabetes Care, 41(2), 277-285. https://doi.org/10.2337/dc17-1080

@article{92893c2ee6624c95ab1c67d0d06a241e,

title = "Interaction of dietary and genetic factors influencing body iron status and risk of type 2 diabetes within the EPIC-InterAct study",

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 (b = 0.113 [95% CI 0.082; 0.144]), but not with transferrin (20.019 [20.043; 0.006]) or transferrin saturation (0.016 [20.006; 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.",

author = "Karina Meidtner and Clara Podmore and Janine Kr{\"o}ger and {Van Der Schouw}, {Yvonne T.} and Benedetta Bendinelli and Claudia Agnoli and Larraitz Arriola and Aurelio Barricarte and Heiner Boeing and Cross, {Amanda J.} and Courtney Dow and Kim Ekblom and Guy Fagherazzi and Franks, {Paul W.} and Gunter, {Marc J.} and Huerta, {Jos{\'e} Mar{\'i}a} and Paula Jakszyn and Mazda Jenab and Katzke, {Verena A.} and Key, {Timothy J.} and Khaw, {Kay Tee} and Tilman K{\"u}hn and Cecilie Kyr{\o} and Mancini, {Francesca Romana} and Olle Melander and Nilsson, {Peter M.} and Kim Overvad and Domenico Palli and Salvatore Panico and {Ram{\'o}n Quir{\'o}s}, J. and Miguel Rodr{\'i}guez-Barranco and Carlotta Sacerdote and Ivonne Sluijs and Magdalena Stepien and Anne Tjonneland and Rosario Tumino and Forouhi, {Nita G.} and Sharp, {Stephen J.} and Claudia Langenberg and Schulze, {Matthias B.} and Elio Riboli and Wareham, {Nicholas J.}",

note = "Funding Information: participants and staff for their contribution to the study and N. Kerrison (Medical Research Council Epidemiology Unit, Cambridge, U.K.) for managing the data for the InterAct Project. The authors thank the participants of the Spanish EPIC cohort for their contribution to the study and the team of trained nurses who participated in the recruitment. EPIC Ragusa is acknowledged for the participation of blood donors of AVIS RAGUSA (local blood donors association). Funding. Funding for the InterAct project was provided by the European Union Sixth Framework Programme (grant no. LSHM_CT_2006_037197). In EPIC Utrecht verification of the Dutch diabetes cases was funded by NL Agency (grant IGE05012) and an Incentive Grant from the UMC Utrecht Board. EPIC Bilthoven and Utrecht acknowledge the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands. EPIC Ragusa acknowledges funding from the Sicilian Regional Government and L{\textquoteright}Associazione Iblea per la Ricerca Epidemiologica (AIRE)-ONLUS di Ragusa. In addition, InterAct investigators acknowledge funding from the following agencies: K.M. and M.B.S.: a grant from the German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD) and the State of Brandenburg; C.P.: Wellcome Trust (grant 097451/Z/11/Z); P.W.F.: Swedish Research Council, Novo Nordisk Foundation, Swedish Diabetes Association, and Swedish Heart-Lung Foundation; J.M.H.: Health Research Fund of the Spanish Ministry of Health, Murcia Regional Government (No. 6236); P.J.: The Health Research Funds RD12/0036/0018 and AGAUR, Generalitat de Catalunya (exp. 2014 SGR 726); V.A.K.: German Cancer Aid, German Federal Ministry of Education and Research (BMBF); T.J. K.: Cancer Research UK; K.T.K.: Medical Research Council UK and Cancer Research UK; T.K.: German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF); P.M.N.: Swedish Research Council; S.P.: Compagnia di San Paolo; J.R.Q.: Government of Principality of Asturias and Regional Government of As-turias; I.S.: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands; A.T.: Danish Cancer Society; and E.R.: Imperial College Biomedical Research Centre. Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions.K.M.conceptualizedthe project, wrote the analysis plan, conducted the statistical analysis, and drafted the manuscript. C.P., J.K., Y.T.v.d.S., B.B., and M.B.S. revised the analysis plan and helped with data interpretation and writing of the manuscript. C.A., L.A., A.B., H.B., A.J.C., C.D.,K.E.,G.F.,P.W.F.,M.J.G.,J.M.H.,P.J.,M.J.,V.A.K., T.J.K., K.T.K., T.K., C.K., F.R.M., O.M., P.M.N., K.O., D.P., S.P., J.R.Q., M.R.-B., C.S., I.S., M.S., A.T., R.T., N.G.F., S.J.S., C.L., E.R., and N.J.W. contributed totheconceptionanddesignofthestudy,interpreta-tionofthedata,andcriticalrevisionofthemanuscript forimportantintellectualcontent.Allauthorsapproved the final version. K.M. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Funding Information: Funding for the InterAct project was provided by the European Union Sixth Framework Programme (grant no. LSHM_CT_2006_037197). In EPIC Utrecht verification of the Dutch diabetes cases was funded by NL Agency (grant IGE05012) and an Incentive Grant from the UMC Utrecht Board. EPIC Bilthoven and Utrecht acknowledge the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands. EPIC Ragusa acknowledges funding from the Sicilian Regional Government and L{\textquoteright}Associazione Iblea per la Ricerca Epidemiologica (AIRE)- ONLUS di Ragusa. In addition, InterAct investigators acknowledge funding from the following agencies: K.M. and M.B.S.: a grant from the German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD) and the State of Brandenburg; C.P.: Wellcome Trust (grant 097451/Z/11/Z); P.W.F.: Swedish Research Council, Novo Nordisk Foundation, Swedish Diabetes Association, and Swedish Heart-Lung Foundation; J.M.H.: Health Research Fund of the Spanish Ministry of Health, Murcia Regional Government (No. 6236); P.J.: The Health Research Funds RD12/0036/0018 and AGAUR, Generalitat de Catalunya (exp. 2014 SGR 726); V.A.K.: German Cancer Aid, German Federal Ministry of Education and Research (BMBF); T.J. K.: Cancer Research UK; K.T.K.: Medical Research Council UK and Cancer Research UK; T.K.: German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF); P.M.N.: Swedish Research Council; S.P.: Compagnia di San Paolo; J.R.Q.: Government of Principality of Asturias and Regional Government of Asturias; I.S.: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands; A.T.: Danish Cancer Society; and E.R.: Imperial College Biomedical Research Centre. Publisher Copyright: {\textcopyright} 2017 by the American Diabetes Association.",

year = "2018",

month = feb,

day = "1",

doi = "10.2337/dc17-1080",

language = "English",

volume = "41",

pages = "277--285",

journal = "Diabetes Care",

issn = "0149-5992",

publisher = "American Diabetes Association Inc.",

number = "2",

}

Meidtner, K, Podmore, C, Kröger, J, Van Der Schouw, YT, Bendinelli, B, Agnoli, C, Arriola, L, Barricarte, A, Boeing, H, Cross, AJ, Dow, C, Ekblom, K, Fagherazzi, G, Franks, PW, Gunter, MJ, Huerta, JM, Jakszyn, P, Jenab, M, Katzke, VA, Key, TJ, Khaw, KT, Kühn, T, Kyrø, C, Mancini, FR, Melander, O, Nilsson, PM, Overvad, K, Palli, D, Panico, S, Ramón Quirós, J, Rodríguez-Barranco, M, Sacerdote, C, Sluijs, I, Stepien, M, Tjonneland, A, Tumino, R, Forouhi, NG, Sharp, SJ, Langenberg, C, Schulze, MB, Riboli, E & Wareham, NJ 2018, 'Interaction of dietary and genetic factors influencing body iron status and risk of type 2 diabetes within the EPIC-InterAct study', Diabetes Care, vol. 41, núm. 2, pàg. 277-285. https://doi.org/10.2337/dc17-1080

TY - JOUR

T1 - Interaction of dietary and genetic factors influencing body iron status and risk of type 2 diabetes within the EPIC-InterAct study

AU - Meidtner, Karina

AU - Podmore, Clara

AU - Kröger, Janine

AU - Van Der Schouw, Yvonne T.

AU - Bendinelli, Benedetta

AU - Agnoli, Claudia

AU - Arriola, Larraitz

AU - Barricarte, Aurelio

AU - Boeing, Heiner

AU - Cross, Amanda J.

AU - Dow, Courtney

AU - Ekblom, Kim

AU - Fagherazzi, Guy

AU - Franks, Paul W.

AU - Gunter, Marc J.

AU - Huerta, José María

AU - Jakszyn, Paula

AU - Jenab, Mazda

AU - Katzke, Verena A.

AU - Key, Timothy J.

AU - Khaw, Kay Tee

AU - Kühn, Tilman

AU - Kyrø, Cecilie

AU - Mancini, Francesca Romana

AU - Melander, Olle

AU - Nilsson, Peter M.

AU - Overvad, Kim

AU - Palli, Domenico

AU - Panico, Salvatore

AU - Ramón Quirós, J.

AU - Rodríguez-Barranco, Miguel

AU - Sacerdote, Carlotta

AU - Sluijs, Ivonne

AU - Stepien, Magdalena

AU - Tjonneland, Anne

AU - Tumino, Rosario

AU - Forouhi, Nita G.

AU - Sharp, Stephen J.

AU - Langenberg, Claudia

AU - Schulze, Matthias B.

AU - Riboli, Elio

AU - Wareham, Nicholas J.

N1 - Funding Information: participants and staff for their contribution to the study and N. Kerrison (Medical Research Council Epidemiology Unit, Cambridge, U.K.) for managing the data for the InterAct Project. The authors thank the participants of the Spanish EPIC cohort for their contribution to the study and the team of trained nurses who participated in the recruitment. EPIC Ragusa is acknowledged for the participation of blood donors of AVIS RAGUSA (local blood donors association). Funding. Funding for the InterAct project was provided by the European Union Sixth Framework Programme (grant no. LSHM_CT_2006_037197). In EPIC Utrecht verification of the Dutch diabetes cases was funded by NL Agency (grant IGE05012) and an Incentive Grant from the UMC Utrecht Board. EPIC Bilthoven and Utrecht acknowledge the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands. EPIC Ragusa acknowledges funding from the Sicilian Regional Government and L’Associazione Iblea per la Ricerca Epidemiologica (AIRE)-ONLUS di Ragusa. In addition, InterAct investigators acknowledge funding from the following agencies: K.M. and M.B.S.: a grant from the German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD) and the State of Brandenburg; C.P.: Wellcome Trust (grant 097451/Z/11/Z); P.W.F.: Swedish Research Council, Novo Nordisk Foundation, Swedish Diabetes Association, and Swedish Heart-Lung Foundation; J.M.H.: Health Research Fund of the Spanish Ministry of Health, Murcia Regional Government (No. 6236); P.J.: The Health Research Funds RD12/0036/0018 and AGAUR, Generalitat de Catalunya (exp. 2014 SGR 726); V.A.K.: German Cancer Aid, German Federal Ministry of Education and Research (BMBF); T.J. K.: Cancer Research UK; K.T.K.: Medical Research Council UK and Cancer Research UK; T.K.: German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF); P.M.N.: Swedish Research Council; S.P.: Compagnia di San Paolo; J.R.Q.: Government of Principality of Asturias and Regional Government of As-turias; I.S.: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands; A.T.: Danish Cancer Society; and E.R.: Imperial College Biomedical Research Centre. Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions.K.M.conceptualizedthe project, wrote the analysis plan, conducted the statistical analysis, and drafted the manuscript. C.P., J.K., Y.T.v.d.S., B.B., and M.B.S. revised the analysis plan and helped with data interpretation and writing of the manuscript. C.A., L.A., A.B., H.B., A.J.C., C.D.,K.E.,G.F.,P.W.F.,M.J.G.,J.M.H.,P.J.,M.J.,V.A.K., T.J.K., K.T.K., T.K., C.K., F.R.M., O.M., P.M.N., K.O., D.P., S.P., J.R.Q., M.R.-B., C.S., I.S., M.S., A.T., R.T., N.G.F., S.J.S., C.L., E.R., and N.J.W. contributed totheconceptionanddesignofthestudy,interpreta-tionofthedata,andcriticalrevisionofthemanuscript forimportantintellectualcontent.Allauthorsapproved the final version. K.M. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Funding Information: Funding for the InterAct project was provided by the European Union Sixth Framework Programme (grant no. LSHM_CT_2006_037197). In EPIC Utrecht verification of the Dutch diabetes cases was funded by NL Agency (grant IGE05012) and an Incentive Grant from the UMC Utrecht Board. EPIC Bilthoven and Utrecht acknowledge the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands. EPIC Ragusa acknowledges funding from the Sicilian Regional Government and L’Associazione Iblea per la Ricerca Epidemiologica (AIRE)- ONLUS di Ragusa. In addition, InterAct investigators acknowledge funding from the following agencies: K.M. and M.B.S.: a grant from the German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD) and the State of Brandenburg; C.P.: Wellcome Trust (grant 097451/Z/11/Z); P.W.F.: Swedish Research Council, Novo Nordisk Foundation, Swedish Diabetes Association, and Swedish Heart-Lung Foundation; J.M.H.: Health Research Fund of the Spanish Ministry of Health, Murcia Regional Government (No. 6236); P.J.: The Health Research Funds RD12/0036/0018 and AGAUR, Generalitat de Catalunya (exp. 2014 SGR 726); V.A.K.: German Cancer Aid, German Federal Ministry of Education and Research (BMBF); T.J. K.: Cancer Research UK; K.T.K.: Medical Research Council UK and Cancer Research UK; T.K.: German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF); P.M.N.: Swedish Research Council; S.P.: Compagnia di San Paolo; J.R.Q.: Government of Principality of Asturias and Regional Government of Asturias; I.S.: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands; A.T.: Danish Cancer Society; and E.R.: Imperial College Biomedical Research Centre. Publisher Copyright: © 2017 by the American Diabetes Association.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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 (b = 0.113 [95% CI 0.082; 0.144]), but not with transferrin (20.019 [20.043; 0.006]) or transferrin saturation (0.016 [20.006; 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.

AB - 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 (b = 0.113 [95% CI 0.082; 0.144]), but not with transferrin (20.019 [20.043; 0.006]) or transferrin saturation (0.016 [20.006; 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.

UR - http://www.scopus.com/inward/record.url?scp=85041220590&partnerID=8YFLogxK

U2 - 10.2337/dc17-1080

DO - 10.2337/dc17-1080

M3 - Article

C2 - 29167213

AN - SCOPUS:85041220590

SN - 0149-5992

VL - 41

SP - 277

EP - 285

JO - Diabetes Care

JF - Diabetes Care

IS - 2

ER -

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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