Dopamine receptor D2 gene polymorphism, urine fluoride, and intelligence impairment of children in China: A school-based cross-sectional study
Dopamine receptor D2 gene polymorphism, urine fluoride, and intelligence impairment of children in China: A school-based cross-sectional study
复制标题
多巴胺受体D2基因多态性、尿氟与中国儿童智力障碍：基于学校的横断面研究
DOI：
10.1016/j.ecoenv.2018.09.018
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发表时间：
2018-12-15
影响因子：
6.8
通讯作者：
Liu, Hongliang
中科院分区：
文献类型：
--
作者：
Cui, Yushan;Zhang, Bin;Liu, Hongliang
目的：我们旨在研究儿童尿氟化物与智商（IQ）的关系，仔细考虑多达30个潜在的混杂因素，以及不同多巴胺受体-2 (DRD2) Taq 1A基因型（CC、CT和TT）儿童尿氟化物水平与智商评分之间的关系可能存在的异质性。方法：采用校本横断面研究设计。采用整群抽样方法，对天津市氟中毒历史流行区和非流行区4所学校的323名儿童（2014-2015年，7-12岁）进行调查。在登记时测量了儿童的尿氟化物水平和特定年龄的智商分数。采用聚合酶链反应-限制性片段长度多态性方法，利用入组时采集的全血基因组DNA对DRD2 Taq 1A多态性进行基因分型。应用多元线性回归模型评估尿氟水平与总体以及DRD2 Taq 1A SNP = CC/CT和TT亚组内智商得分之间的关系。通过自举法、敏感性分析和交叉验证技术测试了模型的稳健性。在TT亚组中确定了尿氟化物水平对智商损害的安全阈值。结果：在所有参与者中，DRD2 Taq 1A多态性本身与尿氟化物水平高的儿童的智商分数无关。在CC/CT亚组中，儿童尿氟化物水平与智商得分无关（校正β（95%置信区间（CI）） = -1.59 (-4.24, 1.05), p = 0.236）。在携带TT基因型的参与者中，对数尿氟化物与儿童智商得分之间存在强烈且稳健的负线性关系(校正β (95% CI) = -12.31 (-18.69, -5.94), p < 0.001)。携带TT基因型的儿童的尿氟化物水平与智商（调整β = -12.31，自举标准误差(SE) = 1.28）的相关性强于总体参与者（调整β = -2.47，自举标准误差(SE) = 3.75） （Z = 2.483，自举p = 0.007）。TT亚组尿氟水平的安全阈值为1.73 mg/L (95% CI = (1.51, 1.97) (mg/L))。结论：不同DRD2 taq1a基因型儿童尿氟与智商的关系存在异质性。需要进行大规模流行病学研究来证实我们的发现。
Objective: We aimed to study the association of urine fluoride with intelligence quotient (IQ) in children with a careful consideration of up to 30 potential confounding factors as well as possible heterogeneity of the relation between urine fluoride levels and IQ scores across children with different dopamine receptor-2 (DRD2) Taq 1A genotypes (CC, CT, and TT).Methods: A school-based cross-sectional study design was applied. A total of 323 children (2014-2015, 7-12 years old) were enrolled from four schools in both historical endemic and non-endemic areas of fluorosis in Tianjin of China using a cluster sampling method. Urine fluoride levels and age-specific IQ scores in children were measured at the enrollment. Polymerase chain reaction-restriction fragment length polymorphism methods were used to genotype DRD2 Taq 1A polymorphism with genomic DNA isolated from whole blood collected at the enrollment. Multiple linear regression models were applied to evaluate the relationship between urine fluoride levels and IQ scores overall and within the DRD2 Taq 1A SNP = CC/CT and TT subgroups. Model robustness was tested through bootstrap, sensitivity analysis, and cross-validation techniques. A safety threshold of urine fluoride levels for IQ impairment was determined in the subgroup TT.Results: In overall participants, the DRD2 Taq 1A polymorphism itself was not related to IQ scores in children who had a high level of urine fluoride. In the CC/CT subgroup, urine fluoride levels and IQ scores in children were unrelated (adjusted beta (95% confidence interval (CI)) = -1.59 (-4.24, 1.05), p = 0.236). Among the participants carrying the TT genotype, there was a strong and robust negative linear relationship between log urine fluoride and IQ scores in children (adjusted beta (95% CI) = -12.31 (-18.69, -5.94), p < 0.001). Urine fluoride levels had a stronger association with IQ in children carrying the TT genotype (adjusted beta = -12.31, bootstrapped standard error (SE) = 1.28), compared to that in overall participants (adjusted beta= -2.47, bootstrapped SE = 3.75) (Z = 2.483 and bootstrapped p = 0.007). The safety threshold of urine fluoride levels in the subgroup TT was 1.73 mg/L (95% CI = (1.51, 1.97) (mg/L)).Conclusions: There is heterogeneity in the relation between urine fluoride and IQ across children carrying different DRD2 Taq 1A genotypes. Large-scale epidemiological studies are needed to confirm our findings.