Papadimitriou G N, Dikeos D G, Karadima G, Avramopoulos D, Daskalopoulou E G, Vassilopoulos D, Stefanis C N
Department of Psychiatry, Eginition Hospital, Athens University Medical School, Greece.
Am J Med Genet. 1998 Feb 7;81(1):73-80.
Genetic factors seem to play an important role in the pathogenesis of affective disorder. The candidate gene strategies are being used, among others, to identify the genes conferring vulnerability to the disease. The genes coding for the receptors of gamma-aminobutyric acid (GABA) have been proposed as candidates for affective disorder, since the GABA neurotransmitter system has been implicated in the pathogenesis of the illness. We examined the possible genetic association between the GABA(A) receptor alpha5 subunit gene locus (GABRA5) on chromosome 15 and affective disorder, in 48 bipolar patients (BP), 40 unipolar patients (UP), and 50 healthy individuals, age- and sex-matched to the patients. All patients and controls were unrelated Greeks. Diagnoses were made after direct interviews according to the DSM-IV and ICD-10 criteria. For the genotyping, a dinucleotide (CA) repeat marker was used. The polymerase chain reaction (PCR) products found were nine alleles with lengths between 272 and 290 base pairs (bp). The distribution of allelic frequencies of the GABRA5 locus differed significantly between BP patients and controls with the 282-bp allele found to be associated with BP affective disorder, while no such difference was observed between the groups of UP patients and controls nor between the two patient groups. The presence or absence of the 282-bp allele in the genotype of BP patients was not shown to influence the age of onset and the overall clinical severity, but was found to be associated with a preponderance of manic over depressive episodes in the course of the illness.
遗传因素似乎在情感障碍的发病机制中起着重要作用。目前正在使用候选基因策略等方法来识别赋予疾病易感性的基因。编码γ-氨基丁酸（GABA）受体的基因已被提议作为情感障碍的候选基因，因为GABA神经递质系统与该疾病的发病机制有关。我们在48例双相情感障碍患者（BP）、40例单相情感障碍患者（UP）和50名年龄及性别与患者匹配的健康个体中，研究了15号染色体上GABA(A)受体α5亚基基因位点（GABRA5）与情感障碍之间可能的遗传关联。所有患者和对照均为无亲缘关系的希腊人。根据《精神疾病诊断与统计手册》第四版（DSM-IV）和《国际疾病分类》第十版（ICD-10）标准，通过直接访谈进行诊断。基因分型采用二核苷酸（CA）重复标记。发现的聚合酶链反应（PCR）产物有9个等位基因，长度在272至290个碱基对（bp）之间。GABRA5位点的等位基因频率分布在BP患者和对照之间存在显著差异，发现282-bp等位基因与BP情感障碍相关，而在UP患者和对照组之间以及两个患者组之间未观察到这种差异。BP患者基因型中282-bp等位基因的有无未显示出会影响发病年龄和总体临床严重程度，但发现在疾病过程中与躁狂发作多于抑郁发作有关。
