精神分裂癥是困擾人類的重大精神疾病之一,，且具有很強(qiáng)的遺傳性,。近年來(lái),，隨著全基因組關(guān)聯(lián)性分析（Genome-wideassociationstudy,GWAS）的逐步開(kāi)展，人們已經(jīng)報(bào)道了一系列的精神分裂癥易感基因,。ZNF804A是最近首先在歐洲人群中通過(guò)病例-對(duì)照研究發(fā)現(xiàn)的一個(gè)精神分裂癥易感基因,。然而，隨后在中國(guó)人群中的驗(yàn)證研究卻報(bào)道了不一致的結(jié)果,。為了探究ZNF804A在中國(guó)人群中是否是精神分裂癥的易感基因,，昆明動(dòng)物研究所宿兵研究員的實(shí)驗(yàn)室（博士研究生李明）通過(guò)與云南省精神病醫(yī)院和玉溪市第二人民醫(yī)院合作，對(duì)這兩個(gè)地區(qū)的2207份病例-對(duì)照樣本進(jìn)行了系統(tǒng)的遺傳學(xué)分析,。
研究發(fā)現(xiàn),，在歐洲人群中報(bào)道的ZNF804A的一個(gè)同精神分裂癥顯著相關(guān)的序列多態(tài)位點(diǎn)（rs1344706）在研究的云南樣本中并不與精神分裂癥相關(guān)。但是,，他們?cè)谇叭藳](méi)有關(guān)注的ZNF804A基因調(diào)控區(qū)卻發(fā)現(xiàn)了兩個(gè)新的相關(guān)位點(diǎn)（rs359895和rs1021042）,。進(jìn)一步的功能實(shí)驗(yàn)證明，在rs359895位點(diǎn)的序列突變會(huì)增強(qiáng)ZNF804A基因調(diào)控區(qū)同廣譜轉(zhuǎn)錄因子Sp1的結(jié)合力,，從而上調(diào)ZNF804A的轉(zhuǎn)錄,。這一結(jié)果同臨床上報(bào)道的精神分裂癥病人大腦中ZNF804A表達(dá)升高的現(xiàn)象是一致的。他們的研究發(fā)現(xiàn)了一個(gè)新的ZNF804A功能突變,。這個(gè)突變可能是中國(guó)人群中導(dǎo)致精神分裂癥發(fā)生的重要遺傳因素之一,。該研究結(jié)果發(fā)表于國(guó)際精神病學(xué)著名刊物《AmericanJournalofPsychiatry》（刊物影響因子，12.76）（生物谷 Bioon.com）
doi:10.1176/appi.ajp.2011.11030381
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PMID:
Allelic Differences Between Han Chinese and Europeans for Functional Variants in ZNF804A and Their Association With Schizophrenia
Ming Li, M.Sc., Xiong-jian Luo, Ph.D., Xiao Xiao, M.Sc., Lei Shi, M.Sc., Xing-yan Liu, M.D., Li-de Yin, M.D., Hong-bo Diao, M.D., and Bing Su, Ph.D.
Objective: ZNF804A is a schizophrenia risk gene that was recently identified by genome-wide association studies as well as subsequent replications. Although the results are consistent among studies in European populations, there have been conflicting reports in Chinese populations. The authors conducted both association and functional analyses to test whether ZNF804A is a risk gene for schizophrenia in Chinese populations. Method: The authors recruited two case-control samples of independent Han Chinese (a total of 2,207 participants) from southwestern China. A total of six single-nucleotide polymorphisms (SNPs), including the key SNP (rs1344706) that showed significant association with schizophrenia in European populations and the other five promoter SNPs of ZNF804A, were tested. Based on the results of the association analysis, the authors performed two functional assays to test the impact of the risk SNP on transcriptional factor binding affinity and promoter activity. Results: The SNP rs1344706 was not associated with schizophrenia in either of the two Han Chinese groups, and this result was confirmed by meta-analyses in five Han Chinese samples. However, the authors identified two ZNF804A promoter SNPs that were significantly associated with schizophrenia in both samples, and the significance was strengthened in the combined samples and further supported by haplotype analysis. The functional assays demonstrated that the risk SNP (rs359895) can influence Sp1 binding affinity, resulting in a higher promoter activity of the risk allele. Conclusions: Our results suggest that ZNF804A is a common risk gene for schizophrenia in world populations and that the newly identified functional SNP (rs359895) is likely a risk SNP for schizophrenia.
