Zhang Sheng-Yu, Hu Qiang, Tang Tao, Liu Chao, Li Cheng-Chong, Yang Xiao-Guang, Zang Yin-Yin, Cai Wei-Xiong
Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Institute of Forensic Science, Ministry of Justice, No. 1347, Guangfu West Road, Putuo District, Shanghai, 200063, People's Republic of China.
Department of Psychology, Qiqihar Mental Health Center, No. 28, Linhua Road, Jianhua District, Qiqihar, 161000, Heilongjiang Province, People's Republic of China.
Neurol Sci. 2017 Aug;38(8):1393-1403. doi: 10.1007/s10072-017-2963-0. Epub 2017 Jun 7.
The study aimed to investigate the correlations of CACNA1C genetic polymorphisms and protein expression with the pathogenesis of schizophrenia in a Chinese population. This research included 139 patients diagnosed with schizophrenia (case group) and 141 healthy volunteers (control group). Case and control samples were genotyped using denaturing high-performance liquid chromatography (DHPLC). Haplotypes of rs10848683, rs2238032, and rs2299661 were analyzed using the Shesis software. A mouse model of schizophrenia was established and assigned to test and blank groups. Western blotting was used to detect CACNA1C protein expression. The genotype and allele distribution of rs2238032 and rs2299661 differed between the case and control groups. TT genotype of rs2238032 and G allele of rs2299661 could potentially reduce the risk of schizophrenia. The distribution of rs2238032 genotype has a close connection with cognitive disturbance and the results of the general psychopathology classification exam. The distribution of rs2299661 genotypes was closely related to sensory and perceptual disorders, negative symptom subscales, and the results of the general psychopathology classification exam. CTC haplotype increased and CTG decreased the risk of schizophrenia in healthy people. In the brain tissues of mice with schizophrenia, the CACNA1C protein expression was higher in the test group than in the blank group. Our study demonstrated that CACNA1C gene polymorphisms and CACNA1C protein expression were associated with schizophrenia and its clinical phenotypes.
该研究旨在探讨中国人群中CACNA1C基因多态性和蛋白表达与精神分裂症发病机制的相关性。本研究纳入了139例被诊断为精神分裂症的患者(病例组)和141名健康志愿者(对照组)。采用变性高效液相色谱法(DHPLC)对病例组和对照组样本进行基因分型。使用Shesis软件分析rs10848683、rs2238032和rs2299661的单倍型。建立精神分裂症小鼠模型并分为试验组和空白组。采用蛋白质印迹法检测CACNA1C蛋白表达。rs2238032和rs2299661的基因型和等位基因分布在病例组和对照组之间存在差异。rs2238032的TT基因型和rs2299661的G等位基因可能会降低精神分裂症的发病风险。rs2238032基因型的分布与认知障碍以及综合精神病理学分类检查结果密切相关。rs2299661基因型的分布与感觉和知觉障碍、阴性症状分量表以及综合精神病理学分类检查结果密切相关。CTC单倍型增加而CTG单倍型降低健康人群患精神分裂症的风险。在精神分裂症小鼠的脑组织中,试验组的CACNA1C蛋白表达高于空白组。我们的研究表明,CACNA1C基因多态性和CACNA1C蛋白表达与精神分裂症及其临床表型相关。