Qi Lu, Meigs James, Manson JoAnn E, Ma Jing, Hunter David, Rifai Nader, Hu Frank B
Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave., Boston, Massachusetts 02115, USA.
Diabetes. 2005 Dec;54(12):3567-72. doi: 10.2337/diabetes.54.12.3567.
To determine whether the HFE gene variants H63D and C282Y are associated with body iron stores and the risk of type 2 diabetes, we conducted a nested case-control study of 714 incident cases of type 2 diabetes and 1,120 matching control subjects in a prospective cohort, the Nurses' Health Study. In both healthy control and diabetic case subjects, H63D homozygosity, C282Y, and the compound heterozygotes were associated with significantly higher levels of plasma ferritin and significantly lower ratios of transferrin receptors to ferritin. Such effects were independent of age, BMI, and lifestyle factors. Overall, there were no significant differences in genotypes of H63D and C282Y between the case and control subjects. A meta-analysis of 4,245 case and 5,982 control subjects indicated a null association of C282Y with diabetes risk, whereas carriers of H63D or the compound heterozygotes had marginally increased risk (odds ratio [OR] 1.11 [95% CI 1.00-1.25] and 1.60 [0.99-2.60], respectively). In addition, we found a significant interaction between HFE variants and heme iron intake (P for interaction = 0.029). The ORs of type 2 diabetes across increasing quartiles of heme iron were 1.00, 1.21 (0.72-2.01), 1.72 (1.03-2.88), and 1.49 (0.91-2.46) among the participants with either the H63D or C282Y variant, whereas the ORs were 1.00, 0.71 (0.49-1.05), 1.12 (0.76-1.66), and 0.96 (0.65-1.42) among those with wild-type genotypes. Our data indicate significant effects of H63D and C282Y on body iron stores and suggest a potential interaction between HFE genotypes and heme iron intake in relation to the risk of type 2 diabetes.
为了确定HFE基因变异体H63D和C282Y是否与体内铁储存及2型糖尿病风险相关，我们在前瞻性队列“护士健康研究”中对714例2型糖尿病新发病例和1120例匹配的对照受试者进行了一项巢式病例对照研究。在健康对照者和糖尿病病例受试者中，H63D纯合子、C282Y以及复合杂合子均与血浆铁蛋白水平显著升高及转铁蛋白受体与铁蛋白的比率显著降低相关。这些效应独立于年龄、体重指数和生活方式因素。总体而言，病例组和对照组之间H63D和C282Y的基因型无显著差异。对4245例病例和5982例对照受试者的荟萃分析表明，C282Y与糖尿病风险无关联，而H63D携带者或复合杂合子的风险略有增加（比值比[OR]分别为1.11[95%可信区间1.00 - 1.25]和1.60[0.99 - 2.60]）。此外，我们发现HFE变异体与血红素铁摄入量之间存在显著交互作用（交互作用P值 = 0.029）。在携带H63D或C282Y变异体的参与者中，随着血红素铁四分位数增加，2型糖尿病的OR值分别为1.00、1.21（0.72 - 2.01）、1.72（1.03 - 2.88）和1.49（0.91 - 2.46），而在野生型基因型参与者中，OR值分别为1.00、0.71（0.49 - 1.05）、1.12（0.76 - 1.66）和0.96（0.65 - 1.42）。我们的数据表明H63D和C282Y对体内铁储存有显著影响，并提示HFE基因型与血红素铁摄入量在2型糖尿病风险方面存在潜在交互作用。
