Piccardi Maria Paola, Ardau Raffaella, Chillotti Caterina, Deleuze Jean Francois, Mallet Jacques, Meloni Rolando, Oi Antonio, Severino Giovanni, Congiu Donatella, Bayorek Michele, Del Zompo Maria
Center of Clinical Psychopharmacology, Department of Neurosciences B.B. Brodie, University of Cagliari, Cagliari, Italy.
Psychiatr Genet. 2002 Mar;12(1):23-7. doi: 10.1097/00041444-200203000-00003.
Association studies with candidate genes may contribute towards the understanding of the etiopathogenesis of bipolar disorder. Candidate genes in bipolar disorders are those related to aminergic neurotransmission, which is the target of the effects of antipsychotics and antidepressants, as well as genes related to signal transduction pathways, reporting the target for the mood-stabilizing effects of lithium. Association with such candidate genes may provide clues towards the understanding of the biological components of bipolar disorder. An association study was performed between the 5' regulatory region of the serotonin transporter gene (5-HTTLPR), the inositol polyphosphate 1-phosphatase gene (INPP1) and bipolar disorder using our sample of proband/parent trios. A total of 101 bipolar probands were considered eligible for the study. Since both parents had to be available, mean age at onset of bipolar disorder in probands was relatively young. However, the mean duration of illness and the number of episodes were consistent with a stable diagnosis. In our trios sample, the transmission disequilibrium test revealed no preferential transmission of alleles of the 5-HTTLPR and INPP1 from heterozygous parents to probands. Therefore, additional family-based data are warranted, possibly with a more complete subdivision of 5-HTTLPR alleles, since short and long alleles have recently been divided into four and six kinds of allelic variant, respectively, with significant ethnic differences in allele and genotype distributions.
对候选基因进行关联研究可能有助于理解双相情感障碍的病因发病机制。双相情感障碍中的候选基因是那些与胺能神经传递相关的基因,胺能神经传递是抗精神病药物和抗抑郁药物作用的靶点,还有与信号转导通路相关的基因,锂盐的心境稳定作用以此为靶点。与这些候选基因的关联可能为理解双相情感障碍的生物学成分提供线索。我们使用先证者/父母三联体样本,对血清素转运体基因(5-HTTLPR)的5'调控区、肌醇多磷酸1-磷酸酶基因(INPP1)与双相情感障碍进行了关联研究。共有101名双相情感障碍先证者被认为符合该研究的条件。由于需要父母双方均参与,先证者中双相情感障碍发病时的平均年龄相对较小。然而,疾病的平均病程和发作次数与稳定的诊断结果相符。在我们的三联体样本中,传递不平衡检验显示5-HTTLPR和INPP1的等位基因从杂合子父母向先证者的传递不存在偏好。因此,有必要获取更多基于家族的数据,可能需要对5-HTTLPR等位基因进行更全面的细分,因为近期短等位基因和长等位基因已分别被细分为四种和六种等位基因变体,等位基因和基因型分布存在显著的种族差异。