Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Diabetes Care. 2018 Feb;41(2):277-285. doi: 10.2337/dc17-1080. Epub 2017 Nov 22.
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.
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.
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 [ H63D], rs1800562 [ C282Y], rs236918 [], rs744653 [], and rs855791 [ 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 ( = 0.16, = 0.21) but did detect a trend toward a negative interaction in men ( = 0.04, = 0.03).
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.
肉类摄入量与 2 型糖尿病的发生呈正相关。这种关联的一部分可能是由身体铁状态介导的，而身体铁状态受遗传因素的影响。我们旨在检验影响身体铁状态的遗传和饮食因素与 2 型糖尿病发生风险之间的相互作用。
该病例-队列研究包括来自 8 个欧洲国家的 9347 例病例和 12301 例亚队列参与者。单核苷酸多态性（SNP）从与铁状态生物标志物相关的全基因组关联研究和候选基因研究中选择。构建了一个与铁蛋白相关的基因评分。使用 Cox 比例风险回归评估血红素铁和 SNP 以及基因评分的乘法和加法相互作用。
更高的血红素铁摄入量（每 1 SD）与更高的铁蛋白水平相关（β=0.113 [95%CI 0.082；0.144]），但与转铁蛋白（-0.019 [-0.043；0.006]）或转铁蛋白饱和度（0.016 [-0.006；0.037]）无关。位于四个基因中的五个 SNP（rs1799945 [H63D]、rs1800562 [C282Y]、rs236918 []、rs744653 []、和 rs855791 [V736A]）与铁蛋白相关。我们没有在整个研究人群中检测到血红素铁和基因评分与糖尿病风险之间的相互作用（ = 0.16， = 0.21），但在男性中检测到一种趋势，即存在负相互作用（ = 0.04， = 0.03）。
我们没有发现令人信服的证据表明，与身体铁状态相关的饮食和遗传因素的相互作用与 2 型糖尿病风险相关，超出了两个单独暴露的总和或乘积所预期的水平。
