Li Chao, Tao Ran, Qin Wei, Zheng Yonglan, He Guang, Shi Yongyong, Li Xingwang, Guo Zhongmeng, Chen Helong, Feng Guoyin, He Lin
Bio-X Life Science Research Center, Shanghai Jiao Tong University, Shanghai, PR China.
Int J Neuropsychopharmacol. 2008 Feb;11(1):27-34. doi: 10.1017/S1461145707007687. Epub 2007 Nov 19.
The PDZ and LIM domain 5 protein (PDLIM5) contains one PDZ (post-synaptic density-95/discs large/zone occludens-1) domain and three LIM (Lin-11, Isl-1, and Mec-3) domains, and is also known as Enigma homologue LIM domain (ENH) protein or LIM protein. DNA microarray analysis of post-mortem brains of schizophrenics has indicated up-regulation of the mRNA level of PDLIM5, and Horiuchi and colleagues reported two single nucleotide polymorphisms (SNPs) (rs2433320 and rs2433322) in the 5' region of the PDZ and LIM domain 5 gene (PDLIM5) to be significantly associated with schizophrenia in the Japanese population. On the other hand, no association with schizophrenia was observed by Kato and colleagues in a different sample of the Japanese population. In this study, we genotyped six SNPs (including rs2433320 and rs2433322) covering PDLIM5 in 507 schizophrenia patients and 530 normal controls recruited from Jiangxi Province, China. Although rs2433320 was negative in our samples, rs2433322 showed significantly different frequencies between cases and controls (P=0.000010). In addition, high linkage disequilibrium was observed between rs2433320 and rs2433322 (D'=0.880), and haplotypes constructed from the two SNPs were significantly associated with schizophrenia (global P=0.00019, even after strict Bonferroni correction). Our results provide further evidence to support PDLIM5 as a potential susceptible gene for schizophrenia.
PDZ和LIM结构域5蛋白（PDLIM5）包含一个PDZ（突触后致密物-95/盘状大蛋白/紧密连接蛋白-1）结构域和三个LIM（Lin-11、Isl-1和Mec-3）结构域，也被称为Enigma同源LIM结构域（ENH）蛋白或LIM蛋白。对精神分裂症患者死后大脑进行的DNA微阵列分析表明，PDLIM5的mRNA水平上调，并且Horiuchi及其同事报道，PDZ和LIM结构域5基因（PDLIM5）5'区域的两个单核苷酸多态性（SNP）（rs2433320和rs2433322）与日本人群中的精神分裂症显著相关。另一方面，Kato及其同事在日本人群的另一个样本中未观察到与精神分裂症的关联。在本研究中，我们对从中国江西省招募的507例精神分裂症患者和530例正常对照中涵盖PDLIM5的六个SNP（包括rs2433320和rs2433322）进行了基因分型。尽管rs2433320在我们的样本中呈阴性，但rs2433322在病例组和对照组之间显示出显著不同的频率（P = 0.000010）。此外，观察到rs2433320和rs2433322之间存在高度连锁不平衡（D' = 0.880），并且由这两个SNP构建的单倍型与精神分裂症显著相关（全局P = 0.00019，即使经过严格的Bonferroni校正）。我们的结果提供了进一步的证据支持PDLIM5作为精神分裂症的潜在易感基因。
