Vogt I R, Shimron-Abarbanell D, Neidt H, Erdmann J, Cichon S, Schulze T G, Müller D J, Maier W, Albus M, Borrmann-Hassenbach M, Knapp M, Rietschel M, Propping P, Nöthen M M
Institute of Human Genetics, University of Bonn, Bonn, Germany.
Am J Med Genet. 2000 Apr 3;96(2):217-21.
Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter that mediates a wide range of central nervous functions by activating multiple 5-HT receptor subtypes. A possible irregularity of serotonergic neurotransmission has been implicated in a variety of neuropsychiatric diseases. In the present study, we performed a systematic mutation scan of the complete coding region and splice junctions of the 5-HT(6) receptor gene to explore the contribution of this gene to the development of bipolar affective disorder and schizophrenia. Investigating 137 unrelated individuals (including 45 bipolar affective patients, 46 schizophrenic patients, and 46 unrelated controls), we identified six single base substitutions (126G/T, 267C/T, 873+30C/T, 873+128A/C, 1128G/C, 1376T/G). Comparing frequencies between patients and controls, we observed a significant overrepresentation of the 267C allele among bipolar patients (P=0. 023 not corrected for multiple testing). This finding was followed up in an independent sample of 105 bipolar family trios using a family-based association design. Fifty-one transmissions could be examined. In 30 cases allele 267C and in 21 cases allele 267T were transmitted to the affected offspring. Although this result was far from statistical significance (transmission disequilibrium test=1.59, P=0.208), the limited number of possible transmissions may have prevented detection of smaller effects. Our preliminary data suggest that bipolar affective disorder may be associated with variation in the 5-HT(6) gene. It will be important to extend the present analysis to larger samples. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:217-221, 2000.
血清素（5-羟色胺，5-HT）是一种神经递质，通过激活多种5-HT受体亚型介导广泛的中枢神经功能。血清素能神经传递的可能异常与多种神经精神疾病有关。在本研究中，我们对5-HT(6)受体基因的完整编码区和剪接位点进行了系统的突变扫描，以探讨该基因在双相情感障碍和精神分裂症发病中的作用。研究了137名无亲缘关系的个体（包括45名双相情感障碍患者、46名精神分裂症患者和46名无亲缘关系的对照），我们鉴定出6个单碱基替换（126G/T、267C/T、873+30C/T、873+128A/C、1128G/C、1376T/G）。比较患者和对照之间的频率，我们观察到双相情感障碍患者中267C等位基因显著过量（P=0.023，未进行多重检验校正）。使用基于家系的关联设计在105个双相情感障碍家系三联体的独立样本中对这一发现进行了后续研究。可以检查51次传递。在30例中，267C等位基因传递给了患病后代；在21例中，267T等位基因传递给了患病后代。尽管这一结果远未达到统计学显著性（传递不平衡检验=1.59，P=0.208），但可能传递的数量有限可能妨碍了对较小效应的检测。我们的初步数据表明，双相情感障碍可能与5-HT(6)基因的变异有关。将目前的分析扩展到更大的样本很重要。《美国医学遗传学杂志》（神经精神遗传学）96:217 - 221，2000年。
