Duan Shiwei, Yin Hua, Chen Wuyan, Xing Qinhe, chen Qi, Guo Tingwei, Gao Jianjun, Li Xiuxia, Gao Rui, Liu Zhuangjun, Gu Niufan, Feng Guoyin, He Lin
Bio-X Life Science Research Center, Shanghai Jiao Tong University, Shanghai 200030, China.
Neurosci Lett. 2005 Mar 11;376(2):93-7. doi: 10.1016/j.neulet.2004.11.028. Epub 2004 Dec 8.
Previous studies have demonstrated that polymorphisms in the putative promoter region of the human serotonin receptor 1B (HTR1B) gene affect gene expression [H.F. Sun, Y.T. Chang, C.S. Fann, C.J. Chang, Y.H. Chen, Y.P. Hsu, W.Y. Yu, A.T. Cheng, Association study of novel human serotonin 5-HT(1B) polymorphisms with alcohol dependence in Taiwanese Han, Biol. Psychiatry 51 (2002) 896-901; J. Duan, A.R. Sanders, J.E. Molen, L. Martinolich, B.J. Mowry, D.F. Levinson, R.R. Crowe, J.M. Silverman, P.V. Gejman, Polymorphisms in the 5'-untranslated region of the human serotonin receptor 1B (HTR1B) gene affect gene expression, Mol. Psychiatry 8 (2003) 901-910]. And the silent mutation G861C allele has been reported to be associated with several psychiatric disorders. Thus, we performed a case-control association study (456 cases and 557 controls) of the five variants in HTR1B gene (T-261G, -182INS/DEL-181, A-161T, C129T and G861C) with schizophrenia. The results showed that neither the allelic distribution nor the major haplotype distribution (except for a rare haplotype) of five SNPs in patients was significantly different from that in controls. A further family-based association study (229 family trios) of G861C allele suggested that HTR1B was not a susceptible gene with schizophrenia in our sample. In conclusion, these data do not support the idea that HTR1B gene plays a major role in the etiopathogenesis of schizophrenia in Chinese Han population.
以往研究表明,人类5-羟色胺受体1B(HTR1B)基因推定启动子区域的多态性会影响基因表达[孙宏发、张育婷、范慈顺、张景杰、陈怡桦、许育鹏、余文耀、郑安涛,台湾汉族人群中新型人类5-羟色胺5-HT(1B)多态性与酒精依赖的关联研究,《生物精神病学》51卷(2002年)第896 - 9月1页;段军、A.R.桑德斯、J.E.莫伦、L.马蒂诺利奇、B.J.莫里、D.F.莱文森、R.R.克罗、J.M.西尔弗曼、P.V.盖伊曼,人类5-羟色胺受体1B(HTR1B)基因5'-非翻译区的多态性影响基因表达,《分子精神病学》8卷(2003年)第901 - 910页]。据报道,沉默突变G861C等位基因与多种精神疾病有关。因此,我们针对HTR1B基因的5个变异位点(T - 261G、- 182INS/DEL - 181、A - 161T、C129T和G861C)进行了一项病例对照关联研究(456例病例和557例对照),以研究其与精神分裂症的关系。结果显示,患者中5个单核苷酸多态性的等位基因分布和主要单倍型分布(除一种罕见单倍型外)与对照组相比均无显著差异。针对G861C等位基因进一步开展的基于家系的关联研究(229个三联家系)表明,在我们的样本中HTR1B基因并非精神分裂症的易感基因。总之,这些数据不支持HTR1B基因在中国汉族人群精神分裂症发病机制中起主要作用这一观点。