Positive association of the serotonin 5-HT7 receptor gene with schizophrenia in a Japanese population
Positive association of the serotonin 5-HT7 receptor gene with schizophrenia in a Japanese population
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DOI：
10.1038/sj.npp.1300901
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发表时间：
2006-04-01
影响因子：
7.6
通讯作者：
Ozaki, N
中科院分区：
文献类型：
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作者：
Ikeda, M;Iwata, N;Ozaki, N
几条证据表明，血清素系统的异常可能与精神分裂症的病理生理学有关。根据结合、动物、尸检和全基因组连锁研究的结果，5-HT 7受体被认为是一种可能的精神分裂症易感因素。在这项研究中，我们进行了连锁不平衡（LD）定位的人类5-HT 7受体基因（HTR 7），并选择了四个“单倍型标签（ht）SNP”。使用这四个htSNPs，我们在383名日本精神分裂症患者和351名对照中进行了LD病例对照关联分析。发现两个htSNPs（SNP 2和SNP 5）和单倍型与精神分裂症相关。在双荧光素酶报告基因测定中进一步评估启动子SNP（SNP 2），但未发现其具有任何功能相关性。虽然我们未能找到一个实际的易感性变异，可以修改HTR 7的功能，我们的研究结果支持的假设，HTR 7是精神分裂症的易感基因在这个种族群体。
Several lines of evidence suggest that abnormalities in the serotonin system may be related to the pathophysiology of schizophrenia. The 5-HT7 receptor is considered to be a possible schizophrenia-susceptibility factor, based on findings from binding, animal, postmortem, and genomewide linkage studies. In this study, we conducted linkage disequilibrium (LD) mapping of the human 5-HT7 receptor gene (HTR7) and selected four 'haplotype-tagging (ht) SNPs'. Using these four htSNPs, we then conducted an LD case-control association analysis in 383 Japanese schizophrenia patients and 351 controls. Two htSNPs (SNP2 and SNP5) and haplotypes were found to be associated with schizophrenia. A promoter SNP ( SNP2) was further assessed in a dual-luciferase reporter assay, but it was not found to have any functional relevance. Although we failed to find an actual susceptibility variant that could modify the function of HTR7, our results support the supposition that HTR7 is a susceptibility gene for schizophrenia in this ethnic group.