Association of the glutamate receptor subunit gene GRIN2B with attention-deficit/hyperactivity disorder
Association of the glutamate receptor subunit gene GRIN2B with attention-deficit/hyperactivity disorder
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DOI：
10.1111/j.1601-183x.2006.00273.x
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发表时间：
2007-07-01
影响因子：
2.5
通讯作者：
Barr, C. L.
中科院分区：
文献类型：
--
作者：
Dorval, K. M.;Wigg, K. G.;Barr, C. L.
谷氨酸能信号通路是注意力缺陷/多动障碍(ADHD)的理想候选易感系统。小鼠特定的N-甲基-D-天冬氨酸型谷氨酸受体亚单位基因(GRIN1，2A-D)的中断会导致认知和/或运动行为的显著改变，包括潜伏性学习、空间记忆任务和多动障碍。在这里，我们通过对205个ADHD先证者确定的核心家系中的9个单核苷酸多态(SNPs)进行基因分型，测试了GRIN2B变异与ADHD的关联。用传递/不平衡检验检测杂合子亲本对患病后代的等位基因传递。使用FBAT程序对ADHD症状维度[注意力不集中(IA)和多动/冲动(HI)]以及言语工作记忆和言语短期记忆的认知测量进行量化性状分析。其中rs2284411的关联最强(chi(2)=7.903，1自由度，P=0.005)。数量性状分析表明，这些标记与ADHD的IA和HI症状维度都有关联，但与言语短期记忆或言语工作记忆的认知指标没有关联。我们的数据表明，GRIN2B亚单位基因的变异与ADHD之间存在联系，无论是分类测量还是数量分布特征。
The glutamatergic signaling pathway represents an ideal candidate susceptibility system for attention-deficit/ hyperactivity disorder (ADHD). Disruption of specific N-methyl-D- aspartate-type glutamate receptor subunit genes (GRIN1, 2A-D) in mice leads to significant alterations in cognitive and/or locomotor behavior including impairments in latent learning, spatial memory tasks and hyperactivity. Here, we tested for association of GRIN2B variants with ADHD, by genotyping nine single nucleotide polymorphisms (SNPs) in 205 nuclear families identified through probands with ADHD. Transmission of alleles from heterozygous parents to affected offspring was examined using the transmission/disequilibrium test. Quantitative trait analyses for the ADHD symptom dimensions [inattentive (IA) and hyperactive/impulsive (HI)] and cognitive measures of verbal working memory and verbal short-term memory were performed using the FBAT program. Three SNPs showed significantly biased transmission (P < 0.05), with the strongest evidence of association found for rs2284411 (chi(2) = 7.903, 1 degree of freedom, P = 0.005). Quantitative trait analyses showed associations of these markers with both the IA and the HI symptom dimensions of ADHD but not with the cognitive measures of verbal short-term memory or verbal working memory. Our data suggest an association between variations in the GRIN2B subunit gene and ADHD as measured categorically or as a quantitatively distributed trait.