5HT2A RECEPTOR PROMOTER POLYMORPHISM, -1438G/A AND SEROTONIN DYSFUNCTION

5HT2A 受体启动子多态性，-1438G/A 和血清素功能障碍

• 批准号: 6431388
• 负责人: MARY ANNE ENOCH
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6431388
• 关键词: anorexia nervosa; clinical research; depression; gene expression; genetic susceptibility; human subject; hypothalamus; neurogenetics; obsessive compulsive disorder; serotonin receptor

Brain serotonin dysfunction is implicated in a range of heritable diseases including alcoholism, mood disorders, eating and obsessive-compulsive (OCD) disorders. An important starting point for understanding innate vulnerability to such diseases is to identify variation in genes involved in serotonin function. The 5-HT2A receptor gene is thought to contribute to appetitive behaviors and to anxiety, and is one site of action of antipsychotics, hallucinogens and anti-depressants. 5-HT2Areceptor densities are higher in individuals with depression and suicide attempts. In this study we replicated an earlier finding of an association of the 5-HT2A promoter polymorphism -1438G/A with anorexia nervosa. In addition we showed that the association extends to OCD but not to bulimia nervosa, a disorder in which obsessive and perfectionistic traits are less manifest (Enoch et al 1998). We have now shown that the promoter polymorphism is associated with OCD in women but not men (Enoch et al, in press, Biol Psychiatry). We have also demonstrated that this 5-HT2A polymorphism is associated with a particular personality type: low novelty seeking and high harm avoidance, again in women but not in men. We have shown an association of the -1438A variant allele with Seasonal Affective Disorder, a condition in which depression recurs in the winter and remits in the spring (Enoch et al 1999). Association studies are being completed in other data sets and preparations are being made for functional studies of this promoter polymorphism.

脑血清素功能障碍与一系列可遗传的疾病有关，包括酒精中毒，情绪障碍，饮食和强迫症（OCD）疾病。了解这种疾病的先天脆弱性的一个重要起点是确定5-羟色胺功能所涉及的基因的变异。 5-HT2A受体基因被认为有助于食欲和焦虑，并且是抗精神病药，致幻剂和抗抑制剂的一个作用部位。抑郁症和自杀企图的个体中，5-HT2受体密度较高。在这项研究中，我们复制了5 -HT2A启动子多态性与神经性厌食的5 -HT2A启动子多态性的关联。此外，我们表明该关联延伸至OCD，但不扩展到神经性贪食症，这种疾病在这种疾病中，强迫症和完美的特征不太明显（Enoch等，1998）。现在，我们已经表明，启动子多态性与女性但男性无性强（Enoch等人，印刷中，生物精神病学）有关）。我们还证明，这种5-HT2A多态性与特定的人格类型有关：在女性中，但在男性中却不是新颖性寻求新颖和高伤害。我们已经显示了-1438A变体等位基因与季节性情感障碍的关联，这种疾病在冬季恢复并在春季汇聚（Enoch等，1999）。协会研究正在其他数据集中完成，并且正在为该启动子多态性的功能研究做准备。