Haplotype Polymorphism in the Alpha-2B-Adrenergic Receptor Gene Influences Response Inhibition in a Large Chinese Sample

Haplotype Polymorphism in the Alpha-2B-Adrenergic Receptor Gene Influences Response Inhibition in a Large Chinese Sample
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DOI:
10.1038/npp.2011.266
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发表时间:
2012-04-01
影响因子:
7.6
通讯作者:
Dong, Qi
Dong, Qi
中科院分区:
医学1区
文献类型:
--
作者:
Lei, Xuemei;Chen, Chuansheng;Dong, Qi

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反应抑制是指抑制不适当或不相关的反应。它在执行功能中起着核心作用,并与广泛的流行神经精神疾病有关。越来越多的神经药理学研究证据表明,去甲肾上腺素神经传递系统中的基因变异对反应抑制有特定贡献。本研究在一个相对较大的健康中国人样本(N = 421)中,对覆盖整个α-2B-肾上腺素能受体(ADRA 2B)基因的5个标签单核苷酸多态性进行基因分型,并研究其与反应抑制的相关性。结果显示ADRA 2B保守单倍型多态性对反应抑制的显著遗传效应,如通过停止信号反应时间(SSRT)测量的(F(2,418)= 5.938,p = 0.003)。AAGG/AAGG基因型个体(n = 89;平均SSRT = 170.2 ms)的SSRT显著短于CCAC/AAGG基因型个体(n = 216;平均SSRT = 182.4 ms;未校正p = 0.03;校正p = 0.09)或CCAC/CCAC基因型个体(n = 116;平均SSRT = 195.8 ms;校正p = 0.09)。
Response inhibition refers to the suppression of inappropriate or irrelevant responses. It has a central role in executive functions, and has been linked to a wide spectrum of prevalent neuropsychiatric disorders. Increasing evidence from neuropharmacological studies has suggested that gene variants in the norepinephrine neurotransmission system make specific contributions to response inhibition. This study genotyped five tag single-nucleotide polymorphisms covering the whole alpha-2B-adrenergic receptor (ADRA2B) gene and investigated their associations with response inhibition in a relatively large healthy Chinese sample (N = 421). The results revealed significant genetic effects of the ADRA2B conserved haplotype polymorphisms on response inhibition as measured by stop-signal reaction time (SSRT) (F(2, 418) = 5.938, p = 0.003). Individuals with the AAGG/AAGG genotype (n = 89; mean SSRT = 170.2 ms) had significantly shorter SSRTs than did those with either the CCAC/AAGG genotype (n = 216; mean SSRT = 182.4 ms; uncorrected p = 0.03; corrected p = 0.09) or the CCAC/CCAC genotype (n = 116; mean SSRT = 195.8 ms; corrected p