Mapping susceptibility loci in attention deficit hyperactivity disorder: preferential transmission of parental alleles at DAT1, DBH and DRD5 to affected children
Mapping susceptibility loci in attention deficit hyperactivity disorder: preferential transmission of parental alleles at DAT1, DBH and DRD5 to affected children
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DOI：
10.1038/sj.mp.4000510
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发表时间：
1999-03-01
影响因子：
11
通讯作者：
Gill, M
中科院分区：
文献类型：
--
作者：
Daly, G;Hawi, Z;Gill, M
注意力缺陷多动障碍(ADHD)是一种常见的儿童障碍，其特征是注意力不集中、运动过度、冲动和注意力分散。它与儿童、青少年和成人的严重残疾有关。(1)这种疾病的病因尚不清楚，但它有很强的遗传成分。(2)在受累儿童及其父母的样本中，我们发现多巴胺转运蛋白(DAT1)基因的多态存在等位基因的优先传递，RR=1.2(1.05-1.37)，P=0.006，再次证实和推广了我们以前的发现：DA1(3)(新样本单尾P=0.039)，多巴胺-β-羟基酶(DBH)，RR=1.31(1.09-1.56)，P=0.0027；多巴胺D5受体，RR=1.67(1.29~2.15)，P=0.00005。DAT1和DBH的关联等位基因在家族性病例中传递较强，RRDAT1=1.29(1.04-1.59)，RRDBH=1.49(1.10-2.00)，而DRD5在非家族性病例中传递较强，RR=1.59(1.05-2.42)。对完整三组的TDT分析支持HHRR分析，对于DAT1 P<；0.005，P<；0.05，对于DRD5，胸径和P<；DAT1、DBH和DRD5的归属分数分别为0.08、0.12和0.20。
Attention deficit hyperactivity disorder (ADHD) is a common disorder of childhood characterized by inattention, excessive motor activity, impulsivity, and distractibility. It is associated with serious disability in children, adolescents and adults.(1) The etiology of the disorder is unknown, but it has a strong genetic component. Pharmacological and biochemical studies have suggested that dopaminergic and noradrenergic systems are involved.(2) Using a sample of affected children and their parents we have found preferential transmission of alleles at polymorphisms at the dopamine transporter (DAT1), RR = 1.2 (1.05-1.37), P = 0.006, re-confirming and extending our previous findings for DAT1(3) (new sample one-tailed P = 0.039); dopamine-beta-hydroxylase (DBH), RR = 1.31 (1.09-1.56), P = 0.0027; and the dopamine D5 receptor (DRD5), RR = 1.67 (1.29-2.15), P = 0.00005. Transmission of the 'associated' alleles at DAT1 and DBH is stronger in familial cases, RRDAT1 = 1.29 (1.04-1.59), RRDBH = 1..49 (1.10-2.00), but for DRD5, transmission is stronger in non-familial cases, RR = 1.59 (1.05-2.42). TDT analysis of complete trios supports the HHRR analysis, with P < 0.05, for DAT1 P < 0.005 and DBH and P < 0.01 for DRD5. Attributable fractions for DAT1, DBH and DRD5 are calculated at 0.08, 0.12 and 0.20 respectively.