围产期风险因素与儿茶酚氧位甲基转移酶和 5-羟色胺转运体基因相互作用可预测 ADHD 患儿的 ASD 症状。
Perinatal risk factors interacting with catechol O-methyltransferase and the serotonin transporter gene predict ASD symptoms in children with ADHD.
机构信息
Department of Psychiatry, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen, The Netherlands.
出版信息
J Child Psychol Psychiatry. 2010 Nov;51(11):1242-50. doi: 10.1111/j.1469-7610.2010.02277.x. Epub 2010 Sep 24.
BACKGROUND
Symptoms of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) often co-occur. Given the previously found familiality of ASD symptoms in children with ADHD, addressing these symptoms may be useful for genetic association studies, especially for candidate gene findings that have not been consistently replicated for ADHD.
METHODS
We studied the association of the catechol O-methyltransferase (COMT) Val158Met polymorphism and the serotonin transporter (SLC6A4/SERT/5-HTT) 5-HTTLPR insertion/deletion polymorphism with ASD symptoms in children with ADHD, and whether these polymorphisms would interact with pre- and perinatal risk factors, i.e., maternal smoking during pregnancy and low birth weight. Analyses were performed using linear regression in 207 Dutch participants with combined type ADHD of the International Multicenter ADHD Genetics (IMAGE) study, and repeated in an independent ADHD sample (n =439) selected from the TRracking Adolescents' Individual Lives Survey (TRAILS). Dependent variables were the total and subscale scores of the Children's Social Behavior Questionnaire (CSBQ).
RESULTS
No significant main effects of COMT Val158Met, 5-HTTLPR, maternal smoking during pregnancy and low birth weight on ASD symptoms were found. However, the COMT Val/Val genotype interacted with maternal smoking during pregnancy in increasing stereotyped behavior in the IMAGE sample (p =.008); this interaction reached significance in the TRAILS sample after correction for confounders (p =.02). In the IMAGE sample, the 5-HTTLPR S/S genotype interacted with maternal smoking during pregnancy, increasing problems in social interaction (p =.02), and also interacted with low birth weight, increasing rigid behavior (p =.03). Findings for 5-HTTLPR in the TRAILS sample were similar, albeit for related CSBQ subscales.
CONCLUSIONS
These findings suggest gene-environment interaction effects on ASD symptoms in children with ADHD.
背景
自闭症谱系障碍（ASD）和注意力缺陷/多动障碍（ADHD）的症状常常同时出现。鉴于先前发现 ADHD 儿童的 ASD 症状具有家族性，解决这些症状可能对遗传关联研究有用，特别是对于 ADHD 候选基因发现尚未得到一致复制的情况。
方法
我们研究了儿茶酚氧位甲基转移酶（COMT）Val158Met 多态性和 5-羟色胺转运体（SLC6A4/SERT/5-HTT）5-HTTLPR 插入/缺失多态性与 ADHD 儿童 ASD 症状的关联，以及这些多态性是否与产前和围产期风险因素相互作用，即母亲怀孕期间吸烟和低出生体重。使用国际多中心 ADHD 遗传学（IMAGE）研究中的 207 名合并型 ADHD 荷兰参与者的线性回归进行分析，并在从青少年个体生活追踪研究（TRAILS）中选择的独立 ADHD 样本（n=439）中重复分析。因变量为儿童社会行为问卷（CSBQ）的总分和分量表得分。
结果
未发现 COMT Val158Met、5-HTTLPR、母亲怀孕期间吸烟和低出生体重对 ASD 症状有显著的主要影响。然而，COMT Val/Val 基因型与母亲怀孕期间吸烟相互作用，增加了 IMAGE 样本中刻板行为（p=0.008）；在对混杂因素进行校正后，这种相互作用在 TRAILS 样本中达到了显著性（p=0.02）。在 IMAGE 样本中，5-HTTLPR S/S 基因型与母亲怀孕期间吸烟相互作用，增加了社交互动问题（p=0.02），也与低出生体重相互作用，增加了僵化行为（p=0.03）。TRAILS 样本中 5-HTTLPR 的结果相似，尽管是针对相关的 CSBQ 分量表。
结论
这些发现表明 ADHD 儿童的 ASD 症状存在基因-环境相互作用效应。
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