Bellgrove Mark A, Hawi Ziarih, Lowe Naomi, Kirley Aiveen, Robertson Ian H, Gill Michael
Department of Psychology and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
Am J Med Genet B Neuropsychiatr Genet. 2005 Jul 5;136B(1):81-6. doi: 10.1002/ajmg.b.30193.
Associations between attention deficit hyperactivity disorder (ADHD) and genetic variants within the dopamine D4 receptor gene have been much reported. Variants investigated include the 7-repeat allele of a VNTR within the third exon, and two SNPs (-521 and -616) located with the promoter region. We investigated the relationship between the VNTR, -521, and -616 SNPs and sustained attention performance in 54 ADHD probands, relative to a non-genotyped control group. Participants performed the Sustained Attention to Response Task (SART) in which the response to an unpredictably occurring target digit must be inhibited. This task, therefore, challenged sustained attention and included a response inhibition component. Consistent with previous reports, ADHD participants possessing the 7-repeat allele of the VNTR outperformed those children not possessing this allele, both in terms of errors and response variability. In family based analyses, better performance on the SART tended to predict biased transmission of the 7-repeat allele from heterozygous parents. For the -521 SNP, A allele homozygotes showed greater impairment than heterozygotes or those not possessing this allele, both in terms of total errors and response variability. Family based analysis showed that higher total errors on the SART predicted transmission of the A allele from heterozygous parents. There were no effects of the -616 SNP. Our results suggest dissociable effects of the "associated alleles" of DRD4 gene variants on sustained attention: while the 7-repeat allele of the VNTR is associated with relatively better performance, the A allele of the -521 SNP is associated with poorer performance.
注意力缺陷多动障碍（ADHD）与多巴胺D4受体基因内的基因变异之间的关联已有大量报道。所研究的变异包括第三外显子内一个可变数目串联重复序列（VNTR）的7重复等位基因，以及位于启动子区域的两个单核苷酸多态性（SNP，-521和-616）。我们研究了54名ADHD先证者中VNTR、-521和-616 SNP与持续注意力表现之间的关系，并与一个未进行基因分型的对照组进行比较。参与者完成持续注意力反应任务（SART），在此任务中，对不可预测出现的目标数字的反应必须被抑制。因此，该任务对持续注意力构成挑战，并包含反应抑制成分。与先前报道一致，拥有VNTR 7重复等位基因的ADHD参与者在错误和反应变异性方面均优于未拥有该等位基因的儿童。在基于家系的分析中，SART上更好的表现倾向于预测7重复等位基因从杂合子父母的偏向性传递。对于-521 SNP，A等位基因纯合子在总错误和反应变异性方面均比杂合子或不拥有该等位基因的个体表现出更大的损伤。基于家系的分析表明，SART上更高的总错误预测了A等位基因从杂合子父母的传递。-616 SNP没有影响。我们的结果表明DRD4基因变异的“相关等位基因”对持续注意力有可分离的影响：虽然VNTR的7重复等位基因与相对较好的表现相关，但-521 SNP的A等位基因与较差的表现相关。
