Association Analyses of MAOA in Chinese Han Subjects with Attention-Deficit/Hyperactivity Disorder: Family-Based Association Test, Case-Control Study, and Quantitative Traits of Impulsivity
Association Analyses of MAOA in Chinese Han Subjects with Attention-Deficit/Hyperactivity Disorder: Family-Based Association Test, Case-Control Study, and Quantitative Traits of Impulsivity
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DOI：
10.1002/ajmg.b.31217
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发表时间：
2011-09-01
影响因子：
2.8
通讯作者：
Wang, Yu-Feng
中科院分区：
文献类型：
--
作者：
Liu, Lu;Guan, Li-Li;Wang, Yu-Feng
单胺氧化酶A（Monoamine oxidase A，MAOA）在5-羟色胺（serotonin，5-HT）、去甲肾上腺素（norepinephrine，NE）和多巴胺（dopamine，DA）等单胺类神经递质的代谢中起着重要作用。遗传研究发现MAOA和注意力缺陷多动障碍（ADHD），特别是冲动之间存在关联。然而，研究之间存在不一致性，这可能是由于ADHD的复杂性和异质性，包括其性二态性和几种亚型的存在。我们在1,253个三人组中进行了传递不平衡检验（TDTs），发现MAOA的5个单核苷酸多态性（SNP）与一般ADHD或主要注意力不集中型（ADHD-I）或混合型（ADHD-C）之间没有关联，但与主要多动/冲动型（ADHD-HI）之间没有关联。与MAOA的关联仅限于男性，尤其是患有ADHD-HI的男性。对1，824例病例和957例对照的数据进行逻辑回归分析，未发现任何相关性。采用协方差分析方法，对640例先证者的MAOA基因型与执行功能行为评定量表（BRIEF）中的“0”因子和810例先证者的Stroop测验成绩进行相关性分析。在TDT测试中发现的风险等位基因纯合子的先证者在BRIEF量表上具有更高的“0”分数，这代表更严重的冲动;该结果也仅限于男性。没有发现与Stroop测试性能的关联。总之，我们的研究结果提供了一些证据，MAOA可能与ADHD-HI亚型，并支持MAOA和冲动之间的关联，这可能是一个潜在的内表型的ADHD。然而，结果受到性别的强烈影响。(C)2011 Wiley-Liss，Inc.
Monoamine oxidase A (MAOA) plays a critical role in the metabolism of monoamine neurotransmitters including serotonin (5-HT), norepinephrine (NE), and dopamine (DA). Genetic studies have found an association between MAOA and attention-deficit/hyperactivity disorder (ADHD), especially impulsivity. However, there has been inconsistency among studies which may be due to the complexity and heterogeneity of ADHD, including its sexual dimorphism and the presence of several subtypes. We conducted transmission disequilibrium tests (TDTs) in 1,253 trios and found no association between five single nucleotide polymorphisms (SNPs) of MAOA with ADHD in general or in the predominantly inattentive (ADHD-I) or combined types (ADHD-C), but with the predominantly hyperactive/impulsivity type (ADHD-HI). The association with MAOA was restricted to males, especially males with ADHD-HI. Logistic regression analyses of data from 1,824 cases and 957 controls did not indicate any association. We used analysis of covariance to analyze the association between MAOA genotype with the "inhibit'' factor of the Behavior Rating Inventory of Executive Function (BRIEF) in 640 probands and performance on the Stroop test in 810 probands. Probands homozygous for risk alleles found in the TDT test had higher "inhibit'' scores on the BRIEF scale which represents more severe impulsivity; this results also was restricted to males. No association was found with Stroop test performance. In conclusion, our results provide some evidence that MAOA may be associated with the ADHD-HI subtype and support the association between MAOA and impulsivity, which may be a potential endophenotype of ADHD. However, the results were strongly influenced by gender. (C) 2011 Wiley-Liss, Inc.