A two-stage case–control association study of PADI2 with schizophrenia
A two-stage case–control association study of PADI2 with schizophrenia
复制标题
DOI：
10.1038/jhg.2009.52
复制
发表时间：
2009-07
影响因子：
3.5
通讯作者：
Yuichiro Watanabe;A. Nunokawa;N. Kaneko;T. Arinami;H. Ujike;T. Inada;N. Iwata;H. Kunugi;M. Itokawa-M.
中科院分区：
文献类型：
--
作者：
Yuichiro Watanabe;A. Nunokawa;N. Kaneko;T. Arinami;H. Ujike;T. Inada;N. Iwata;H. Kunugi;M. Itokawa-M.
肽基精氨酸脱亚胺酶 (PADI) 已鉴定出五种亚型，可催化蛋白质中精氨酸残基转化为瓜氨酸残基。最近的研究表明，PADI2（该基因在整个神经系统中表达）的异常激活可能与具有神经退行性过程的神经精神疾病（例如阿尔茨海默病和多发性硬化症）的发病机制有关。这种进行性神经退行性过程可能涉及精神分裂症的病因和/或病程，而PADI2可能是精神分裂症的候选基因。为了评估 PADI2 是否与精神分裂症易感性有关，我们在日本个体中进行了一项两阶段病例对照关联研究。在 534 名患者和 559 名对照个体的筛查人群中，我们检查了 PADI2 中的 8 个单核苷酸多态性 (SNP)，包括 4 个单倍型标签 SNP 和 4 个编码 SNP。外显子 7 中的同义 SNP 与精神分裂症存在潜在关联。然而，我们无法在 2126 名患者和 2228 名对照个体的验证人群中复制这种关联。这项研究的结果表明，PADI2 不会导致精神分裂症的遗传易感性。
Peptidylarginine deiminases (PADIs), five isoforms of which have been identified, catalyze the conversion of arginine residues to citrulline residues in proteins. Recent studies have revealed that abnormal activation of PADI2, the gene for which is expressed throughout the nervous system, is likely to be related to the pathogenesis of neuropsychiatric diseases with neurodegenerative processes, such as Alzheimer's disease and multiple sclerosis. Such a progressive neurodegenerative process could be involved in the etiology and/or course of schizophrenia, and PADI2 may be a candidate gene for schizophrenia. To assess whether PADI2 has a role in vulnerability to schizophrenia, we conducted a two-stage case–control association study in Japanese individuals. In a screening population of 534 patients and 559 control individuals, we examined eight single-nucleotide polymorphisms (SNPs) including four haplotype tag SNPs and four coding SNPs in PADI2. There was a potential association of a synonymous SNP in exon 7 with schizophrenia. However, we could not replicate this association in a confirmatory population of 2126 patients and 2228 control individuals. The results of this study suggest that PADI2 does not contribute to genetic susceptibility to schizophrenia.