Gene expression and association analyses of LIM (PDLIM5) in bipolar disorder and schizophrenia
Gene expression and association analyses of LIM (PDLIM5) in bipolar disorder and schizophrenia
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DOI：
10.1038/sj.mp.4001719
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发表时间：
2005-11-01
影响因子：
11
通讯作者：
Yoshikawa, T
中科院分区：
文献类型：
--
作者：
Kato, T;Iwayama, Y;Yoshikawa, T
我们以前报道过，LIM（ENH，PDLIM5）的表达水平在双相情感障碍，精神分裂症和抑郁症患者的大脑中显着和普遍增加。双相情感障碍和精神分裂症患者的淋巴母细胞样细胞中LIM的表达降低。据报道，LIM蛋白在连接蛋白激酶C与钙通道中起重要作用。这些发现表明LIM在双相情感障碍和精神分裂症的病理生理学中的作用。为了进一步研究LIM在这些精神障碍中的作用，我们进行了基因表达分析的复制研究，并进行了遗传关联研究。在从Stanley Array Collection获得的独立样品组中证实了LIM的上调。未观察到样品pH值或药物的影响。遗传关联研究显示单核苷酸多态性（SNP）1（rs10008257）与双相情感障碍相关。在一个独立的样本集中，SNP2（rs2433320）接近SNP1与双相情感障碍。在总样本中，这两个SNP的单倍型与双相情感障碍相关。在精神分裂症的病例对照分析和以家庭为基础的关联分析中未观察到关联。这些结果表明，单核苷酸多态性在上游区域的LIM可能赋予双相情感障碍的遗传风险。
We previously reported that expression level of LIM (ENH, PDLIM5) was significantly and commonly increased in the brains of patients with bipolar disorder, schizophrenia, and major depression. Expression of LIM was decreased in the lymphoblastoid cells derived from patients with bipolar disorders and schizophrenia. LIM protein reportedly plays an important role in linking protein kinase C with calcium channel. These findings suggested the role of LIM in the pathophysiology of bipolar disorder and schizophrenia. To further investigate the role of LIM in these mental disorders, we performed a replication study of gene expression analysis and performed genetic association studies. Upregulation of LIM was confirmed in the independent sample set obtained from Stanley Array Collection. No effect of sample pH or medication was observed. Genetic association study revealed the association of single nucleotide polymorphism ( SNP) 1 ( rs10008257) with bipolar disorder. In an independent sample set, SNP2 (rs2433320) close to SNP1 was associated with bipolar disorder. In total samples, haplotype of these two SNPs was associated with bipolar disorder. No association was observed in case - control analysis and family-based association analysis in schizophrenia. These results suggest that SNPs in the upstream region of LIM may confer the genetic risk for bipolar disorder.