Nyman Emma S, Ogdie Matthew N, Loukola Anu, Varilo Teppo, Taanila Anja, Hurtig Tuula, Moilanen Irma K, Loo Sandra K, McGough James J, Järvelin Marjo-Riitta, Smalley Susan L, Nelson Stanley F, Peltonen Leena
National Public Health Institute, Helsinki, Finland.
J Am Acad Child Adolesc Psychiatry. 2007 Dec;46(12):1614-21. doi: 10.1097/chi.0b013e3181579682.
Attention-deficit/hyperactivity disorder (ADHD) is a common childhood-onset disorder with a significant impact on public health. Although a genetic contribution to risk is evident, predisposing genetic determinants remain largely unknown despite extensive research. So far, the most promising candidate genes have been those involved in dopamine and serotonin pathways. This study tests a series of allelic variants within such candidate genes to determine their potential influence on ADHD susceptibility.
We used a population sample ascertained from a birth cohort of a subpopulation of Finland, characterized by founder effect and isolation, thus minimizing genetic heterogeneity. The subjects were systematically ascertained using DSM-IV diagnostic criteria for ADHD from the Northern Finland Birth Cohort 1986 of more than 9,000 individuals, resulting in the study sample of 188 ADHD cases and 166 controls. We genotyped markers in 13 candidate genes, including critical components of dopamine and serotonin pathways.
We report evidence for association of ADHD with allelic variants of the dopamine beta-hydroxylase (DBH) and dopamine receptor D2 (DRD2) genes.
Our study supports the involvement of the dopamine pathway in the etiology of ADHD; specifically the genes DBH and DRD2 deserve more attention in further studies.
注意力缺陷多动障碍(ADHD)是一种常见的儿童期起病的疾病,对公众健康有重大影响。尽管遗传因素对风险的影响显而易见,但尽管进行了广泛研究,易患ADHD的遗传决定因素仍大多未知。到目前为止,最有希望的候选基因是那些参与多巴胺和血清素途径的基因。本研究测试了这些候选基因中的一系列等位基因变体,以确定它们对ADHD易感性的潜在影响。
我们使用了从芬兰一个亚人群的出生队列中确定的人群样本,该样本具有奠基者效应和隔离特征,从而最大限度地减少了遗传异质性。使用《精神疾病诊断与统计手册》第四版(DSM-IV)对来自1986年芬兰北部出生队列的9000多名个体进行ADHD诊断标准的系统确定,从而得到了188例ADHD病例和166例对照的研究样本。我们对13个候选基因中的标记进行了基因分型,包括多巴胺和血清素途径的关键成分。
我们报告了ADHD与多巴胺β-羟化酶(DBH)和多巴胺受体D2(DRD2)基因的等位基因变体之间存在关联的证据。
我们的研究支持多巴胺途径参与ADHD的病因学;具体而言,DBH和DRD2基因在进一步研究中值得更多关注。