Gene expression and association analysis of LIM (PDLIM5) in major depression
Gene expression and association analysis of LIM (PDLIM5) in major depression
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DOI：
10.1016/j.neulet.2006.02.044
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发表时间：
2006-06-12
影响因子：
2.5
通讯作者：
Ohmori, Tetsuro
中科院分区：
文献类型：
--
作者：
Iga, Jun-ichi;Ueno, Shu-ichi;Ohmori, Tetsuro
LIM(PDLIM5)是一种与蛋白激酶C-epsilon和N型钙通道α-1B亚基相互作用并调节神经元钙信号的小蛋白。近年来，LIM基因在心境障碍患者死后脑和永生化淋巴母细胞中的表达发生了改变，并可能参与了其病理生理过程。我们推测，LIM mRNA在自然外周血白细胞中的表达可能是一个很好的情绪性障碍的生物标志物。20名重度抑郁症患者和年龄和性别匹配的对照组受试者参加了这项表达研究。药物治疗后抑郁症患者外周血白细胞中LIM基因表达水平显著低于对照组，帕罗西汀治疗4周后LIM基因表达水平显著升高，接近对照组水平。治疗4周后，汉密尔顿抑郁评分(HAM-D)改善约50%，但帕罗西汀浓度和HAM-D评分的变化与mRNA水平的变化均无显着相关性。然后，我们对LIM基因的三个单核苷酸多态标记进行了基因分型，这些标记被报道与重度抑郁症患者和对照组(n=130)的双相情感障碍有关，但这些SNPs与重度抑郁症没有关联。我们的研究表明，外周血白细胞LIM mRNA的低表达与抑郁状态有关，其治疗后的恢复可能是抗抑郁药物诱导的适应性变化。(C)2006爱思唯尔爱尔兰有限公司。保留所有权利。
LIM (PDLIM5) is a small protein that interacts with protein kinase C-epsilon and the N-type calcium channel alpha-1B subunit and modulates neuronal calcium signaling. Recently, the LIM mRNA expression in postmortem brains and immortalized lymphoblastoid cells from mood disorder patients was reported to be changed and seems to be involved in its pathophysiology. We hypothesized that the expression of the LIM mRNA in the native peripheral leukocytes may be a good candidate for the biological marker for mood disorders. Twenty patients with major depression and age- and sex-matched control subjects were included in this expression study. The LIM mRNA levels in the peripheral leukocytes from drug-naive depressive patients were significantly lower than those from control subjects and increased significantly after 4-week paroxetine treatments, to almost the same level as controls'. Hamilton depressive scores (HAM-D) were improved about 50% after 4-week treatment but neither paroxetine concentrations nor the changes of HAM-D scores showed significant correlation with the change of the mRNA levels. Then, we genotyped three single nucleotide polymorphic markers of LIM gene, which were reported to be associated with bipolar disorder in patients with major depression and control subjects (n = 130, each), but there were no associations between these SNPs and major depression. Our investigation indicates that the lower expression levels of LIM mRNA in the peripheral leukocytes are associated with the depressive state and that its recovery after treatment may be an adaptive change induced by the antidepressant. (c) 2006 Elsevier Ireland Ltd. All rights reserved.