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台湾样本中,单胺氧化酶A基因与注意力缺陷多动障碍的关联研究。

Association study between the monoamine oxidase A gene and attention deficit hyperactivity disorder in Taiwanese samples.

作者信息

Xu Xiaohui, Brookes Keeley, Chen Chih-Ken, Huang Yu-Shu, Wu Yu-Yu, Asherson Philip

机构信息

MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.

出版信息

BMC Psychiatry. 2007 Feb 28;7:10. doi: 10.1186/1471-244X-7-10.

Abstract

BACKGROUND

Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable disorder of childhood characterized by inattention, hyperactivity and impulsivity. Molecular genetic and pharmacological studies suggest the involvement of the dopaminergic, serotonergic and noradrenergic neurotransmitter systems in the pathogenesis of ADHD. Monoamine oxidase A (MAO-A) encodes an enzyme that degrades biogenic amines, including neurotransmitters such as norepinephrine, dopamine and serotonin. In this study we examined a 30 bp promoter variable number tandem repeat (VNTR) and a functional G/T single nucleotide polymorphism (SNP) at position 941 in exon 8 (941G/T) of MAO-A for association with ADHD in a Taiwanese sample of 212 ADHD probands.

METHODS

Within-family transmission disequilibrium test (TDT) was used to analyse association of MAO-A polymorphisms with ADHD in a Taiwanese population.

RESULTS

A nominally significant association was found between the G-allele of 941G/T in MAO-A and ADHD (TDT: P = 0.034. OR = 1.57). Haplotype analysis identified increased transmission of a haplotype consisting of the 3-repeat allele of the promoter VNTR and the G-allele of the 941G/T SNP (P = 0.045) to ADHD cases which the strong association with the G-allele drove.

CONCLUSION

These findings suggest the importance of the 941G/T MAO-A polymorphism in the development of ADHD in the Taiwanese population. These results replicate previously published findings in a Caucasian sample.

摘要

背景

注意力缺陷多动障碍(ADHD)是一种常见且具有高度遗传性的儿童疾病,其特征为注意力不集中、多动和冲动。分子遗传学和药理学研究表明,多巴胺能、血清素能和去甲肾上腺素能神经递质系统参与了ADHD的发病机制。单胺氧化酶A(MAO-A)编码一种可降解生物胺的酶,这些生物胺包括去甲肾上腺素、多巴胺和血清素等神经递质。在本研究中,我们在一个包含212名ADHD先证者的台湾样本中,检测了MAO-A基因外显子8中941位的30 bp启动子可变数目串联重复序列(VNTR)和功能性G/T单核苷酸多态性(SNP)与ADHD的关联性。

方法

采用家系内传递不平衡检验(TDT)分析台湾人群中MAO-A基因多态性与ADHD的关联性。

结果

发现MAO-A基因941G/T位点的G等位基因与ADHD之间存在名义上显著的关联性(TDT:P = 0.034,OR = 1.57)。单倍型分析确定,由启动子VNTR的3重复等位基因和941G/T SNP的G等位基因组成的单倍型向ADHD病例的传递增加(P = 0.045),这是由与G等位基因的强关联性驱动的。

结论

这些发现表明941G/T MAO-A基因多态性在台湾人群ADHD发病过程中的重要性。这些结果重复了先前在白种人样本中发表的研究结果。

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