Variants in iron metabolism genes predict higher blood lead levels in young children.
Variants in iron metabolism genes predict higher blood lead levels in young children.
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铁代谢基因的变异预示着幼儿的血铅水平较高。
DOI：
10.1289/ehp.11233
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发表时间：
2008-09
影响因子：
10.4
通讯作者：
Wright RO
中科院分区：
文献类型：
--
作者：
Hopkins MR;Ettinger AS;Hernández-Avila M;Schwartz J;Téllez-Rojo MM;Lamadrid-Figueroa H;Bellinger D;Hu H;Wright RO
鉴于铁缺乏和铅吸收之间的关联，我们假设铁代谢基因的变异将预测幼儿血铅水平较高。我们研究了422名墨西哥儿童血色病（HFE）和转铁蛋白（TF）基因中常见的错义变异与血铅水平之间的关系。对存档的脐带血样本进行HFE（H63 D和C282 Y）和TF（P570 S）变体的基因分型。在24、30、36、42和48个月大时测量血铅。共有341名受试者至少有一次随访血铅水平可用，并有相关协变量的数据可纳入纵向分析。我们使用随机效应模型来研究基因型（HFE、TF和HFE + TF组合）与血铅重复测量之间的关联，校正分娩时母亲血铅和儿童并发贫血状态。在422名基因分型的儿童中，分别有17.7%、3.3%和18.9%携带HFE H63 D、HFE C282 Y和TF P570 S变异体。1%的儿童同时携带HFE C282 Y和TF P570 S变体，3%的儿童同时携带HFE H63 D和TF P570 S变体。平均而言，携带HFE（β = 0.11，p = 0.04）或TF（β = 0.10，p = 0.08）变体的受试者的血铅水平分别比野生型受试者高11%和10%。在检查剂量效应的模型中，携带两种变体的受试者（β = 0.41，p = 0.006）的血铅比野生型受试者高50%，血铅水平> 10 μg/dL的几率显着更高（比值比= 18.3; 95%置信区间，1.9-177.1）。铁代谢基因变异改变铅代谢，使得HFE变异与幼儿血铅水平升高相关。HFE和TF基因中的变异等位基因的联合存在显示出最大的影响，表明基因与基因与环境的相互作用。
Given the association between iron deficiency and lead absorption, we hypothesized that variants in iron metabolism genes would predict higher blood lead levels in young children. We examined the association between common missense variants in the hemochromatosis (HFE) and transferrin (TF) genes and blood lead levels in 422 Mexican children. Archived umbilical cord blood samples were genotyped for HFE (H63D and C282Y) and TF (P570S) variants. Blood lead was measured at 24, 30, 36, 42, and 48 months of age. A total of 341 subjects had at least one follow-up blood lead level available and data available on covariates of interest for inclusion in the longitudinal analyses. We used random-effects models to examine the associations between genotype (HFE, TF, and combined HFE + TF) and repeated measures of blood lead, adjusting for maternal blood lead at delivery and child’s concurrent anemia status. Of 422 children genotyped, 17.7, 3.3, and 18.9% carried the HFE H63D, HFE C282Y, and TF P570S variants, respectively. One percent of children carried both the HFE C282Y and TF P570S variants, and 3% of children carried both the HFE H63D and TF P570S variants. On average, carriers of either the HFE (β = 0.11, p = 0.04) or TF (β = 0.10, p = 0.08) variant had blood lead levels that were 11% and 10% higher, respectively, than wild-type subjects. In models examining the dose effect, subjects carrying both variants (β = 0.41, p = 0.006) had blood lead 50% higher than wild-type subjects and a significantly higher odds of having a blood lead level > 10 μg/dL (odds ratio = 18.3; 95% confidence interval, 1.9–177.1). Iron metabolism gene variants modify lead metabolism such that HFE variants are associated with increased blood lead levels in young children. The joint presence of variant alleles in the HFE and TF genes showed the greatest effect, suggesting a gene-by-gene-by-environment interaction.
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影响因子：
10.4
作者：
Onalaja, AO;Claudio, L
通讯作者：
Claudio, L
影响因子：
8
作者：
Gomaa, A;Hu, H;Hernandez-Avila, M
通讯作者：
Hernandez-Avila, M
影响因子：
11.2
作者：
Guilarte, TR;Toscano, CD;Weaver, SA
通讯作者：
Weaver, SA
影响因子：
7.1
作者：
HALLBERG, L;ROSSANDERHULTEN, L
通讯作者：
ROSSANDERHULTEN, L
影响因子：
2.9
作者：
Bradley, LA;Johnson, DD;Ferrie, RM
通讯作者：
Ferrie, RM