Gene Expression and Association Analyses of the Phosphodiesterase 4B (PDE4B) Gene in Major Depressive Disorder in the Japanese Population
Gene Expression and Association Analyses of the Phosphodiesterase 4B (PDE4B) Gene in Major Depressive Disorder in the Japanese Population
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DOI：
10.1002/ajmg.b.30852
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发表时间：
2009-06-05
影响因子：
2.8
通讯作者：
Ohmori, Tetsuro
中科院分区：
文献类型：
--
作者：
Numata, Shusuke;Iga, Jun-ichi;Ohmori, Tetsuro
磷酸二酯酶 4B (PDE4B) 与精神分裂症中断 1 (DISC1) 相互作用，DISC1 是精神分裂症、双相情感障碍和重度抑郁症 (MDD) 的已知遗传风险因素。 PDE4B 在 cAMP 信号传导的调节中也很重要，cAMP 信号传导是与学习、记忆和情绪有关的第二信使。在这项研究中，我们测定了 MDD 患者和对照受试者（各 n = 33）外周血白细胞中 PDE4B 基因的 mRNA 表达水平。接下来，我们在日本人群中进行了两阶段病例对照关联分析（第一组；病例 = 174，对照 = 348；第二组；病例 = 481，对照 = 812），以确定 PDE4B 基因是否与 MDD 有关。在白细胞中，与对照组相比，未接受药物治疗的 MDD 患者的 PDE4B mRNA 表达显着升高（P < 0.0001），而抗抑郁治疗后 MDD 患者的表达显着降低（P = 0.030）。在关联分析中，我们在第一组样本中观察到四个 SNP（最显着的 rs472952；P = 0.002）的显着等位基因关联以及 PDE4B 基因和 MDD 之间的显着单倍型关联（排列 P = 0.019）。然而，我们无法在以下独立的第二组样本中证实这些显着关联。我们的结果表明，PDE4B 基因本身与 MDD 无关，但 PDE4B mRNA 水平升高可能与 MDD 的病理生理学有关。 (C) 2008 Wiley-Liss, Inc.
The phosphodiesterase 4B (PDE4B) interacts with disrupted-in-schizophrenia 1 (DISC1), which is a known genetic risk factor for schizophrenia, bipolar disorder and major depressive disorder (MDD). PDE4B is also important in the regulation of cAMP signaling, a second messenger implicated in learning, memory, and mood. In this study, we determined mRNA expression levels of the PDE4B gene in the peripheral blood leukocytes of patients with MDD and control subjects (n = 33, each). Next we performed two-stage case-controlled association analyses (first set; case = 174, controls = 348; second set; case = 481, controls = 812) in the Japanese population to determine if the PDE4B gene is implicated in MDD. In the leukocytes, a significantly higher expression of the PDE4B mRNA was observed in the drug-naive MDD patients compared with control subjects (P < 0.0001) and the expression of the MDD patients significantly decreased after antidepressant treatment (P = 0.030). In the association analysis, we observed significant allelic associations of four SNPs (the most significant, rs472952; P = 0.002) and a significant haplotypic association (permutation P = 0.019) between the PDE4B gene and MDD in the first-set samples. However, we could not confirm these significant associations in the following independent second-set of samples. Our results suggest that the PDE4B gene itself does not link to MDD but the elevated mRNA levels of PDE4B might be implicated in the pathophysiology of MDD. (C) 2008 Wiley-Liss, Inc.