Department of Clinical Neuroscience Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Bipolar Disord. 2011 Aug-Sep;13(5-6):500-8. doi: 10.1111/j.1399-5618.2011.00952.x.
Several genetic loci have been suggested to be associated with bipolar disorder but results have been inconsistent. Studying associations between bipolar symptoms and candidate genes may better expose this relationship. Here we investigate the association between bipolar key symptoms and the P2RX7 gene.
Key symptoms of mania were rated in two sets of medicated bipolar disorder patients (n=171 and n=475) at two specialized outpatient clinics for affective disorders and three regular psychiatric outpatient units in Sweden. The relationships between all manic symptoms according to DSM-IV were entered in a principal component analysis. We used a case-case model to reduce the genetic heterogeneity and tested associations between four factors related to manic symptoms and their association to four single nucleotide polymorphisms in the P2RX7 gene.
The combination of the cognitive symptoms, distractibility, talkativeness, and thought disorder was significantly associated with rs1718119 in the P2RX7 gene in Set 1 [odds ratio (OR) = 1.78; p=0.011]. The association was re-tested in the second set (OR = 1.42; p=0.009). In the total sample, the association was even stronger (OR = 1.49; p<0.001). None of the other factors was associated with the P2RX7 gene. Within the first factor, the distractibility symptom accounted for a significant portion of the association to rs1718119 (p=0.016).
There is an association between specific symptoms of bipolar disorder and the P2RX7 gene. This finding may open up new approaches to elucidating the neurobiology behind bipolar symptoms.
有几个遗传位点被认为与双相情感障碍有关，但结果并不一致。研究双相情感障碍症状与候选基因之间的关系可能更好地揭示这种关系。在这里，我们研究了双相情感障碍关键症状与 P2RX7 基因之间的关系。
在瑞典的两个专门的情感障碍门诊和三个常规精神病门诊单位，对两组接受药物治疗的双相情感障碍患者（n=171 和 n=475）进行了躁狂关键症状的评定。根据 DSM-IV 评定的所有躁狂症状均进入主成分分析。我们使用病例-病例模型来减少遗传异质性，并测试了与躁狂症状相关的四个因素与 P2RX7 基因的四个单核苷酸多态性之间的关联。
认知症状、注意力不集中、多话和思维障碍的组合在 Set1 中与 P2RX7 基因中的 rs1718119 显著相关（OR=1.78;p=0.011）。在第二组中重新进行了测试（OR=1.42;p=0.009）。在总样本中，相关性更强（OR=1.49;p<0.001）。没有其他因素与 P2RX7 基因相关。在第一个因素中，注意力不集中症状与 rs1718119 的关联占显著部分（p=0.016）。
双相情感障碍的特定症状与 P2RX7 基因之间存在关联。这一发现可能为阐明双相情感障碍症状背后的神经生物学机制开辟新途径。
