Kahn Robert S, Khoury Jane, Nichols William C, Lanphear Bruce P
Division of General and Community Pediatrics, and Children's Environmental Health Center, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
J Pediatr. 2003 Jul;143(1):104-10. doi: 10.1016/S0022-3476(03)00208-7.
To examine the joint effects of a dopamine transporter (DAT) polymorphism and maternal prenatal smoking on childhood hyperactivity-impulsivity and inattentiveness.
A cohort of 161 children was followed prospectively from age 6 months to 60 months. Primary outcomes were the DSM-IV hyperactive-impulsive and inattentive scales of the Conners' Parent Rating Scale Revised-Long Version (CPRS R:L). A secondary outcome was the oppositional scale. Predictors included DAT genotype and maternal report of prenatal smoking. Children homozygous for the 480-bp DAT allele (DAT +/+) were compared with all other children (DAT +/- or -/-).
In multivariate analyses, children with both prenatal smoke exposure and the DAT +/+ genotype had significantly elevated hyperactive-impulsive scores (beta, 7.5; SE, 2.9; P<.01) compared with children with no smoke exposure and DAT +/- or -/-. Inattentive scores were not significantly elevated in this group, but oppositional scores were a full standard deviation higher. Neither prenatal smoke exposure alone nor DAT +/+ genotype alone was significantly associated with increased scores.
Child hyperactivity-impulsivity and oppositional behaviors were associated with a DAT polymorphism but only when the child also had exposure to maternal prenatal smoking. This study emphasizes the importance of incorporating environmental cofactors in genetic studies of attention deficit hyperactivity disorder.
研究多巴胺转运体（DAT）基因多态性与母亲孕期吸烟对儿童多动冲动及注意力不集中的联合影响。
对161名儿童进行前瞻性随访，从6个月至60个月。主要结局指标为《康纳斯父母评定量表修订版长式》（CPRS R:L）中DSM-IV多动冲动和注意力不集中分量表。次要结局指标为对立违抗分量表。预测因素包括DAT基因型和母亲报告的孕期吸烟情况。将携带480 bp DAT等位基因纯合子的儿童（DAT +/+）与所有其他儿童（DAT +/-或-/-）进行比较。
在多变量分析中，与未暴露于吸烟且为DAT +/-或-/-的儿童相比，既暴露于孕期吸烟又为DAT +/+基因型的儿童多动冲动得分显著升高（β值为7.5；标准误为2.9；P <.01）。该组儿童注意力不集中得分未显著升高，但对立违抗得分高出整整一个标准差。单独的孕期吸烟暴露或单独的DAT +/+基因型均与得分升高无显著关联。
儿童多动冲动及对立违抗行为与DAT基因多态性有关，但仅在儿童同时暴露于母亲孕期吸烟时才出现。本研究强调了在注意力缺陷多动障碍基因研究中纳入环境协同因素的重要性。
