Human 5-HT1A receptor C(-1019)G polymorphism and psychopathology
Human 5-HT1A receptor C(-1019)G polymorphism and psychopathology
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DOI：
10.1017/s1461145704004663
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发表时间：
2004-12-01
影响因子：
4.8
通讯作者：
Mann, JJ
中科院分区：
文献类型：
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作者：
Huang, YY;Battistuzzi, C;Mann, JJ
5-羟色胺(5-HT1A)受体(5-HTR1A)功能障碍与情绪障碍、焦虑症、精神病和抗抑郁药的作用有关。人类5-HT1A受体基因启动子区域常见的C(-1018)G[C(-1019)G]功能多态性已被报道，这可能有助于识别与人类5-HT1A受体功能改变相关的精神病理学。我们研究了该基因多态性与精神病理和前额叶皮质5-HT1a结合的关系。对696例无血缘关系的精神病患者、107例无血缘关系的健康志愿者和241例尸脑标本进行了C(-1019)G多态的5-HT1A受体基因分型。用[H-3]8-OH-DPAT测定死后前额叶皮质5-HT1a受体的结合，用1um 5-HT1测定5-HT1a受体的特异性结合。5-HTR1AC(-1019)G基因座的等位基因频率与精神分裂症(x(2)=9.51，D.F.)相关。=2，p=0.009；x(2)=9.52D.F.=1，p=0.002；阿米蒂奇趋势检验：X(2)=9.07D.F.=1，p=0.003)，物质使用障碍(x(2)=8.41，D.F.=2，p=0.015；x(2)=8.35，D.F.=1，p=0.004；阿米蒂奇趋势测验：x(2)=6.27，D.F.=1，p=0.0012)；惊恐发作(x(2)=6.31，D.F.=2，p=0.043；x(2)=6.14，D.F.=1，p=0.013；阿米蒂奇趋势检验：x(2)=6.27，D.F.=1，p=0.012)。我们的结果提示5-HTR1AC(-1019)G基因座与精神分裂症、物质使用障碍和惊恐发作有关。在死后脑标本中，前额叶皮质5-HT1a受体结合和自杀与基因频率无关。这种关系似乎不能用结合差异来解释，尽管我们不能排除受体亲和力和转导的改变。
Dysfunction of the serotonin (5-HT1A) receptor (5-HTR1A) has been implicated in mood disorders, anxiety disorders, psychosis and the action of antidepressants. A common C(-1018)G [C(-1019)G] functional polymorphism in the promoter region of the human 5-HT1A receptor gene has been reported, which may be useful in identifying psychopathology associated with altered function of the human 5-HT1A receptor. We studied the relationship of this polymorphism to psychopathology and 5-HT1A binding in prefrontal cortex. The 5-HT1A receptor genotype for the C(-1019)G polymorphism was typed in 696 unrelated psychiatric subjects, 107 unrelated healthy volunteers, and in post-mortem brain samples from 241 cases. 5-HT1A receptor binding was assayed in post-mortem prefrontal cortex using [H-3]8-OH-DPAT, and specific binding determined by 1 mum 5-HT. An association of genotype distribution and allele frequency of the 5-HTR1A C(-1019)G locus was observed in schizophrenia (x(2) = 9.51, d.f. = 2, p = 0.009; x(2) = 9.52, d.f. = 1, p = 0.002; Armitage's trend test: x(2) = 9.07, d.f. = 1, p = 0.003), in substance use disorder (x(2) = 8.41, d.f.=2, p = 0.015; x(2) = 8.35, d.f.=1, p = 0.004; Armitage's trend test: x(2) = 6.27, d.f.=1, p = 0.0012), and in panic attack (x(2) = 6.31, d.f.=2, p = 0.043; x(2) = 6.14, d.f.=1, p = 0.013; Armitage's trend test: x(2) = 6.27, d.f.=1, p = 0.012). An association of the 5-HTR1A C(-1019)G locus with schizophrenia, substance use disorder, and panic attack was suggested by our results. In post-mortem brain samples, 5-HT1A receptor binding in prefrontal cortex and suicide were not associated with genotype. The relationship does not appear to be explained by binding differences, although we cannot rule out altered receptor affinity and transduction.