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首页> 外文期刊>Pharmacogenetics and genomics >Stargazin involvement with bipolar disorder and response to lithium treatment.
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Stargazin involvement with bipolar disorder and response to lithium treatment.

机译：Stargazin参与双相情感障碍和对锂治疗的反应。

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OBJECTIVES: Multiple reports have implicated chromosomal region 22q13.1 in both schizophrenia and bipolar disorder. The calcium channel gamma-2 subunit gene (cacng2, Stargazin) located on 22q13.1 was recently reported to be associated with schizophrenia. We aimed to examine the expression levels of Stargazin in post-mortem brain samples of patients with schizophrenia, patients with bipolar disorder (BPD) and healthy controls, test for genetic association between Stargazin and these disorders and test for genetic association between Stargazin and response to lithium treatment. METHODS: Expression analysis was carried out by quantitative reverse transcription-PCR in RNA samples from dorsolateral prefrontal cortices of patients with schizophrenia, patients with BPD and controls (n=35 each). Twelve single nucleotide polymorphisms encompassing Stargazin were genotyped in DNA samples from two cohorts, 'Aberdeen' and 'Cagliari' (n=410, 170, respectively). Patients were treated with lithium and divided into groups according to their response. RESULTS: A 1.6-fold overexpression of Stargazin was observed in patients with BPD (P=0.000036). No difference in expression was observed in patients with schizophrenia. None of the 12 genotyped single nucleotide polymorphisms were associated with BPD, but three of them were significantly associated with lithium response: one in both cohorts (rs2284017) and two (rs2284018, rs5750285) each in a different cohort. Haplotype analysis revealed significant 'response-protective' and 'response-inhibitive' haplotypes in both cohorts. CONCLUSION: Our findings suggest that Stargazin dysregulation may be involved with the pathophysiology of BPD, but not with that of schizophrenia, and that Stargazin polymorphisms may play a role in the response to lithium treatment.
机译：目的：多个报告都暗示精神分裂症和双相情感障碍的染色体区域22q13.1。最近报道了位于22q13.1的钙通道gamma-2亚基基因（cacng2，Stargazin）与精神分裂症有关。我们的目的是检查精神分裂症患者，双相情感障碍（BPD）患者和健康对照者的死后脑样本中Stargazin的表达水平，测试Stargazin与这些疾病之间的遗传关联，以及测试Stargazin与反应之间的遗传关联锂处理。方法：通过定量逆转录PCR对精神分裂症患者，BPD患者和对照组（n = 35）的背外侧前额叶皮层RNA样品进行表达分析。在来自两个队列“阿伯丁”和“卡利亚里”（分别为n = 410、170）的DNA样本中对包含Stargazin的十二个单核苷酸多态性进行了基因分型。患者接受锂治疗，并根据反应分为几组。结果：在BPD患者中观察到Stargazin的1.6倍过表达（P = 0.000036）。在精神分裂症患者中未观察到表达差异。 12个基因型单核苷酸多态性均未与BPD相关，但其中三个与锂反应显着相关：两个队列中的一个（rs2284017）和两个队列中的（rs2284018，rs5750285）每个都在不同队列中。单倍型分析显示在两个队列中都有显着的“反应保护型”和“反应抑制型”单倍型。结论：我们的发现表明，Stargazin失调可能与BPD的病理生理有关，但与精神分裂症无关，并且Stargazin的多态性可能在锂治疗的反应中起作用。

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