Toenail arsenic concentrations, GSTT1 gene polymorphisms, and arsenic exposure from drinking water

Toenail arsenic concentrations, GSTT1 gene polymorphisms, and arsenic exposure from drinking water
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DOI:
10.1158/1055-9965.epi-05-0306
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发表时间:
2005-10-01
影响因子:
3.8
通讯作者:
Christiani, DC
Christiani, DC
中科院分区:
医学3区
文献类型:
--
作者:
Kile, ML;Houseman, EA;Christiani, DC

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在孟加拉国砷流行地区居住的人群中,将脚趾甲砷 (As) 浓度作为无机砷 (As-in) 暴露的生物标志物进行评估。持续 2 年,每 3 个月从 48 个家庭 (n = 223) 收集饮用水和脚趾甲样本,并使用电感耦合等离子体质谱法分析砷。将每次脚趾甲样本采集前 3、6 和 9 个月收集的饮用水合并为加权滞后暴露变量。每个水样对测量的脚趾甲 As 浓度的贡献是使用最大似然估计的,该最大似然考虑了饮用水暴露和脚趾甲生长的波动。最佳模型将 69%、14% 和 17% 的趾甲砷含量归因于采集趾甲前 3、6 和 9 个月发生的饮用水暴露 [95% 置信区间 (95%n CI) 分别为 0.46-0.97、0.00-0.31 和 0.03-0.35]。采用使用惩罚回归样条的广义加性混合模型对数据进行建模。低于 2 μg As/L 的饮用水浓度,没有观察到饮用水 As 和脚趾甲 As 浓度之间的关系。高于这个浓度,脚趾甲砷含量随着饮用水砷的增加而以剂量依赖性方式增加。年龄是饮用水砷暴露对趾甲砷暴露的显着影响因素(0 = 0.01;95% CI,0.002-0.02)。与GSTT1野生型个体相比,具有GSTT1无效基因型的个体在脚趾甲中具有显着更多的As(β=0.11;95%CI,0.06-0.2)。因此,GSTT1 似乎改变了 Asin 暴露与脚趾甲 Asin 含量之间的关系。
Toenail arsenic (As) concentrations were evaluated as a biomarker of inorganic As (As-in) exposure in a population residing in an As-endemic region of Bangladesh. Drinking water and toenail samples were collected from 48 families (n = 223) every 3 months for 2 years and analyzed for As using inductively coupled plasma-mass spectrometry. Drinking water collected 3, 6, and 9 months before each toenail sample collection was combined into a weighted lagged exposure variable. The contribution of each water sample to the measured toenail As concentration was estimated using maximum likelihood that accounted for fluctuations in drinking water exposure and toenail growth. The best model attributed 69%, 14%, and 17% of the toenail As content to drinking water exposures that occurred 3, 6, and 9 months before toenail collection [95% confidence intervals (95%n CI), 0.46-0.97, 0.00-0.31, and 0.03-0.35, respectively]. Generalized additive mixed models using penalized regression splines were employed to model the data. Below a drinking water concentration of 2 mu g As/L, no relationship between drinking water As and toenail As concentrations was observed. Above this concentration, toenail As content increased in a dose-dependent fashion as drinking water As increased. Age was a significant effect modifier of drinking water As exposure on toenail As (0 = 0.01; 95% CI, 0.002-0.02). Individuals possessing GSTTl-null genotypes had significantly more As in their toenails in contrast to GSTT1 wild-type individuals (beta = 0.11; 95% CI, 0.06-0.2). Therefore, it seems that GSTT1 modifies the relationship between Asin exposure and toenail Asin content.