Zhang Chen, Wang Zuowei, Hong Wu, Wu Zhiguo, Peng Daihui, Fang Yiru
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Mol Neurobiol. 2016 Jul;53(5):2936-2943. doi: 10.1007/s12035-015-9193-3. Epub 2015 May 3.
Genetic variation in the gene encoding zinc finger protein 804A gene (ZNF804A) has been identified to be associated with bipolar disorder in genome-wide association studies, while little is known regarding their association in Asian populations. In this study, we aimed to examine whether ZNF804A may confer susceptibility to BD in Han Chinese. We measured the mRNA expression level of ZNF804A in patients with BD and controls. Two functional variants (rs1344706 and rs359895) in ZNF804A were genotyped among 1508 individuals with or without BD. We then performed a meta-analysis based on present literature. Our results showed that ZNF804A mRNA level in peripheral blood mononuclear cells was significantly higher in BD patients than that in controls (P = 0.01). The rs1344706 showed significant allelic association with BD (P = 0.034). The frequency of T allele of rs1344706 was higher in patients than that in controls (odds ratio = 1.19, 95 % confidence interval 1.03-1.37). After pooling all data, meta-analysis indicated a significant association of rs1344706 with BD (P = 0.0003). Furthermore, we performed an eQTL analysis and observed significant associations between rs1344706 and ZNF804A expression level in hippocampus (P = 0.032) and occipital cortex (P = 0.036). After stratified by diagnosis, the association of rs1344706 with BD was only survived in BD-I (genotypic P = 0.04, allelic P = 0.014), but not in BD-II. Our findings provided supportive evidence for the involvement of ZNF804A rs1344706 in BD, especially in BD-I.
在全基因组关联研究中，已确定编码锌指蛋白804A基因（ZNF804A）的基因变异与双相情感障碍有关，而关于其在亚洲人群中的关联知之甚少。在本研究中，我们旨在研究ZNF804A是否可能使汉族人群易患双相情感障碍。我们测量了双相情感障碍患者和对照组中ZNF804A的mRNA表达水平。在1508名有或无双相情感障碍的个体中对ZNF804A中的两个功能变异（rs1344706和rs359895）进行了基因分型。然后我们基于现有文献进行了荟萃分析。我们的结果表明，双相情感障碍患者外周血单个核细胞中的ZNF804A mRNA水平显著高于对照组（P = 0.01）。rs1344706与双相情感障碍存在显著的等位基因关联（P = 0.034）。rs1344706的T等位基因频率在患者中高于对照组（优势比= 1.19，95%置信区间1.03 - 1.37）。汇总所有数据后，荟萃分析表明rs1344706与双相情感障碍存在显著关联（P = 0.0003）。此外，我们进行了表达定量性状位点（eQTL）分析，观察到rs1344706与海马体（P = 0.032）和枕叶皮质（P = 0.036）中ZNF804A表达水平之间存在显著关联。按诊断分层后，rs1344706与双相情感障碍的关联仅在双相I型障碍中存在（基因型P = 0.04，等位基因P = 0.014），而在双相II型障碍中不存在。我们的研究结果为ZNF804A rs1344706参与双相情感障碍，尤其是双相I型障碍提供了支持性证据。
