Laboratory of Psychoneuroendocrinology and Molecular Genetics, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria, Martín Lagos s/n 28040, Madrid, Spain.
Schizophr Bull. 2013 May;39(3):555-63. doi: 10.1093/schbul/sbr176. Epub 2012 Jan 31.
NR4A2 (nuclear receptor subfamily 4 group A member 2) or Nurr1 is a transcription factor implied in the differentiation, maturation, and survival of dopaminergic neurons. It also has a role in the expression of several proteins that are necessary for the synthesis and regulation of dopamine (DA), such as tyrosine hidroxilase, dopamine transporter, vesicular monoamine transporter 2, and cRET. DA is an important neurotransmitter in attentional pathways. Our aim was to evaluate the influence of NR4A2 gene in the performance of schizophrenia (SZ) patients and healthy subjects on a sustained attention task. For this study, we collected 188 SZ subjects (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and 100 control individuals. We genotyped 5 tag SNPs in NR4A2 gene: rs1150143 (C/G), rs1150144 (A/G), rs834830 (A/G), rs1466408 (T/A), and rs707132 (A/G). We also analyzed the influence of its haplotypes (frequency>5%). To examine sustained attention, all the individuals completed the Degraded Stimulus Continuous Performance Test. We evaluated "hits," "reaction time," "sensibility a," and "false alarms." In the schizophrenic group, recessive genotypes of rs1150143, rs1150144, rs834830, and rs707132 were associated with a worse performance. SZ subjects who carried GGGTG haplotype showed less hits (P<.004), lower sensibility a scores (P<.009), and a higher reaction time (P=.013). We observed a sex effect of the gene: genotype and haplotype associations were only present in the male group. We conclude that NR4A2 gene is involved in attentional deficits of SZ patients, modifying hits, sensibility a, and reaction time.
NR4A2（核受体亚家族 4 组 A 成员 2）或 Nurr1 是一种转录因子，参与多巴胺能神经元的分化、成熟和存活。它在几种蛋白质的表达中也发挥作用，这些蛋白质对于多巴胺（DA）的合成和调节是必要的，如酪氨酸羟化酶、多巴胺转运体、囊泡单胺转运体 2 和 cRET。DA 是注意力通路中的一种重要神经递质。我们的目的是评估 NR4A2 基因对精神分裂症（SZ）患者和健康受试者在持续注意力任务中的表现的影响。为此，我们收集了 188 名 SZ 患者（精神障碍诊断和统计手册，第四版）和 100 名对照个体。我们对 NR4A2 基因中的 5 个标签 SNP 进行了基因分型：rs1150143（C/G）、rs1150144（A/G）、rs834830（A/G）、rs1466408（T/A）和 rs707132（A/G）。我们还分析了其单倍型（频率>5%）的影响。为了检查持续注意力，所有个体都完成了退化刺激连续绩效测试。我们评估了“命中”、“反应时间”、“敏感性 a”和“假警报”。在精神分裂症组中，rs1150143、rs1150144、rs834830 和 rs707132 的隐性基因型与较差的表现相关。携带 GGGTG 单倍型的 SZ 患者的命中次数较少（P<.004），敏感性 a 评分较低（P<.009），反应时间较长（P=.013）。我们观察到基因的性别效应：基因型和单倍型关联仅存在于男性组中。我们得出结论，NR4A2 基因参与 SZ 患者的注意力缺陷，改变了命中次数、敏感性 a 和反应时间。
