金嘉郦刘璐李海梅高倩王玉凤钱秋谨

·论 著·

CLOCK基因与睡眠对男性注意缺陷多动障碍患儿注意抑制的影响☆

金嘉郦*刘璐*李海梅*高倩*王玉凤*钱秋谨*

目的 探讨生物钟（clock circadian regulator，CLOCK）基因与男性儿童注意缺陷多动障碍（atten⁃tion-deficit/hyperactivity disorder，ADHD）的关联，以及CLOCK基因与睡眠问题及其交互作用对ADHD男性患儿注意抑制的影响。方法 对854例ADHD男性患儿与320名男性对照儿童的CLOCK基因rs6832769与rs11932595单核苷酸多态性位点（single nucleotide polymorphisms，SNPs）进行基因型检测。采用Conners父母症状问卷评估ADHD组与对照组的睡眠问题，通过Stroop色词命名测验评估ADHD组的注意抑制功能，通过协方差分析分别检验CLOCK基因2个SNPs和睡眠问题及其交互作用对ADHD男性患儿注意抑制的影响。结果rs6832769、rs11932595的等位基因频率、基因型频率与ADHD的关联均无统计学意义（P＞0.05）。rs6832769、rs11932595基因型及睡眠问题对男性ADHD患儿注意抑制的主效应均没有统计学意义（P＞0.05）；rs6832769基因型与睡眠问题对注意抑制存在交互作用（F=6.71，P=0.01），伴睡眠问题且携带rs6832769位点AG&GG基因型患者的字义干扰时更长（F=6.63，P=0.01）。结论 CLOCK基因rs6832769与睡眠问题可能存在交互作用，共同影响ADHD男性患儿的注意抑制功能。

注意缺陷多动障碍 睡眠 基因 反应抑制

【Abstract】Objective To explore the correlation between circadian clock gene clock circadian regulator（CLOCK）and attention-deficit/hyperactivity disorder（ADHD）and the role of CLOCK and sleep problems on inhibition in male children with ADHD.Methods Two single nucleotide polymorphisms（SNPs）of CLOCK were genotyped in 854 male ADHD children and 320 male controls.Sleep problems were assessed using parent symptom questionnaire.In ADHD cases，the main effects and interaction of CLOCK SNPs and sleep problems on inhibition assessed by using Stroop Color and Word Test，were analyzed using the analysis of covariance（ANCOVA）.Results No significant differences of allele and genotype frequencies were found for rs6832769 and rs11932595 in all case-control groups（P＞0.05）.In ADHD cas⁃es，the main effects of rs6832769 and rs11932595 genotypes and sleep problems on inhibition were not significant（P＞0.05）.However，the interaction of rs6832769 genotype and sleep problems was significant（F=6.71，P=0.01）.When ac⁃companied with sleep problems，ADHD cases carrying the AA&AG genotype showed the longest time of word interfer⁃ence（F=6.63，P=0.01）.Conclusions Inhibition of male ADHD children can be modulated by the interaction of CLOCK rs6832769 and sleep problems.

【Key words】Attention-deficit/hyperactivity disorder SleepGene Reactive inhibition

注意缺陷多动障碍（attention-deficit/hyperac⁃tivity disorder，ADHD）起病于儿童期，是常见的神经发育障碍性疾病之一，患病率约为5%［1］。ADHD具有高度遗传性，遗传度约为0.76［2］，遗传异质性强，是多基因遗传的复杂疾病。既往分子遗传学研究提示，生物钟（clock circadian regulator，CLOCK）基因CLOCK 3’非翻译区的单核苷酸多态性位点（single nucleotide polymorphisms，SNP）rs1801260与ADHD及其症状存在关联［3-5］。而睡眠是受到生物钟调控的主要行为之一，ADHD患者常常伴有睡眠问题，表现为睡眠抵抗、入睡困难、早起困难等［6］。……