DNA pooling analysis of 21 norepinephrine transporter gene SNPs with attention deficit hyperactivity disorder: No evidence for association

被引:40
作者
Xu, XH [1 ]
Knight, J [1 ]
Brookes, K [1 ]
Mill, J [1 ]
Sham, P [1 ]
Craig, I [1 ]
Taylor, E [1 ]
Asherson, P [1 ]
机构
[1] Kings Coll London, MRC Social Genet & Dev Psychiat Ctr, Inst Psychiat, London WC2R 2LS, England
关键词
norepinephrine; polymorphisms; ADHD; DNA pooling; association study;
D O I
10.1002/ajmg.b.30160
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The norepinephrine system is known to play a role in attentional and cognitive-energetic mechanisms and is thought to be important in attention deficit hyperactivity disorder (ADHD). Stimulant medications are known to alter the activity of norepinephrine as well as dopamine in the synapse and the highly selective norepinephrine reuptake inhibitor, atomoxetine, is an effective treatment for ADHD symptoms. This study set out to investigate whether common polymorphisms within the norepinephrine transporter gene (NET1) are associated with DSM-IV ADHD combined subtype, using a sample that has previously shown association with genes that affect the synaptic release and uptake of neurotransmitters; DAT1 and SNAP-25. We identified 21 single nucleotide polymorphisms (SNPs) from publicly available databases that had minor allele frequencies >= 5% and span the NET1 genomic region, including those analyzed in previous studies of ADHD. DNA pooling was used to screen for associations using two case pools (n = 180 cases) and four control pools (n = 334 controls). We identified three SNPs that showed suggestive evidence for association using either case-control or within family tests of association, however, none of these were significant after adjustment for the number of markers analyzed. We conclude that none of the markers show significant evidence of association with ADHD although we cannot rule out small genetic effects. (c) 2005 Wiley-Liss, Inc.
引用
收藏
页码:115 / 118
页数:4
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