氟暴露、多巴胺相对基因多态性与智力：中国的一项横断面研究。
Fluoride exposure, dopamine relative gene polymorphism and intelligence: A cross-sectional study in China.
机构信息
Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing 100191, PR China; Institute of Environment and Health, Tianjin Centers for Disease Control and Prevention, Tianjin 300011, PR China.
Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing 100191, PR China.
出版信息
Ecotoxicol Environ Saf. 2021 Feb;209:111826. doi: 10.1016/j.ecoenv.2020.111826. Epub 2020 Dec 24.
BACKGROUND
Excessive fluoride exposure is related to adverse health outcomes, but whether dopamine (DA) relative genes are involved in the health effect of low-moderate fluoride exposure on children's intelligence remain unclear.
OBJECTIVES
We conducted a cross-sectional study to explore the role of DA relative genes in the health effect of low-moderate fluoride exposure in drinking water.
METHODS
We recruited 567 resident children, aged 6-11 years old, randomly from endemic and non-endemic fluorosis areas in Tianjin, China. Spot urine samples were tested for urinary fluoride concentration, combined Raven`s test was used for intelligence quotient test. Fasting venous blood were collected to analyze ANKK1 Taq1A (rs1800497), COMT Val158Met (rs4680), DAT1 40 bp VNTR and MAOA uVNTR. Multivariable linear regression models were used to assess associations between fluoride exposure and IQ scores. We applied multiplicative and additive models to appraise single gene-environment interaction. Generalized multifactor dimensionality reduction (GMDR) was used to evaluate high-dimensional interactions of gene-gene and gene-environment.
RESULTS
In adjusted model, fluoride exposure was inversely associated with IQ scores (β = -5.957, 95% CI: -9.712, -2.202). The mean IQ scores of children with high-activity MAOA genotype was significantly lower than IQ scores of those with low-activity (P = 0.006) or female heterozygote (P = 0.016) genotype. We detected effect modification by four DA relative genes (ANKK1, COMT, DAT1 and MAOA) on the association between UF and IQ scores. We also found a high-dimensional gene-environment interaction among UF, ANKK1, COMT and MAOA on the effect of IQ (testing balanced accuracy = 0.5302, CV consistency: 10/10, P = 0.0107).
CONCLUSIONS
Our study suggests DA relative genes may modify the association between fluoride and intelligence, and a potential interaction among fluoride exposure and DA relative genes on IQ.
背景
过量的氟暴露与不良健康结果有关，但多巴胺（DA）相关基因是否参与低-中度氟暴露对儿童智力的健康影响尚不清楚。
目的
我们进行了一项横断面研究，以探讨 DA 相关基因在饮用水中低-中度氟暴露对健康的影响。
方法
我们从中国天津市地方性和非地方性氟中毒地区随机招募了 567 名 6-11 岁的常住儿童。采集尿样检测尿氟浓度，采用联合瑞文氏测验进行智商测验。采集空腹静脉血，分析 ANKK1 Taq1A（rs1800497）、COMT Val158Met（rs4680）、DAT1 40bpVNTR 和 MAOA uVNTR。采用多变量线性回归模型评估氟暴露与智商得分之间的关系。我们应用乘法和加法模型来评估单基因-环境交互作用。广义多因子降维（GMDR）用于评估基因-基因和基因-环境的高维交互作用。
结果
在调整模型中，氟暴露与智商得分呈负相关（β=-5.957，95%CI：-9.712，-2.202）。高活性 MAOA 基因型儿童的平均智商得分明显低于低活性（P=0.006）或女性杂合子（P=0.016）基因型儿童。我们检测到四个 DA 相关基因（ANKK1、COMT、DAT1 和 MAOA）对 UF 和 IQ 得分之间的关联有修饰作用。我们还发现 UF、ANKK1、COMT 和 MAOA 之间存在高维的基因-环境相互作用，对 IQ 有影响（检验平衡准确性=0.5302，CV 一致性：10/10，P=0.0107）。
结论
我们的研究表明，DA 相关基因可能修饰氟与智力之间的关联，以及氟暴露与 DA 相关基因对 IQ 的潜在相互作用。
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