洪汉林段秀荣刘婵媛

L型钙离子通道α1C亚基基因多态性与精神分裂症的相关性

洪汉林*段秀荣*刘婵媛*

目的 探讨L型钙离子通道α1C亚基（calcium channel，voltage-dependent，L type，alpha 1C subunit，CACNA1C）基因多态性与精神分裂症的关系。 方法 纳入118例精神分裂症患者及122名对照，采用变性高效液相色谱法对其CACNA1C基因rs10848683、rs2238032、rs2299661位点进行基因分型，通过病历资料收集患者感知觉障碍、思维障碍、情感障碍和行为障碍等临床表现，采用阳性与阴性症状量表（positive and negative syn⁃drome scale，PANSS）评估患者症状。 结果 rs2238032和rs2299661位点基因型和等位基因在患者组与对照组间分布有统计学差异（均P＜0.05），而rs10848683位点基因型和等位基因分布在组间无统计学差异（P＞0.05）。rs2238032位点TT基因型（OR=0.394）和rs2299661位点CG（OR=0.326）与精神分裂症的患病风险有关联（均P＜0.05）。rs10848683位点各基因型患者行为障碍分布有统计学差异（P＜0.05）；rs2238032各基因型患者思维障碍、情感障碍和PANSS得分有统计学差异（均P＜0.05）；rs2299661各基因型患者感知觉障碍、PANSS得分有统计学差异（均P＜0.05）。单体型分析示，CTC（OR=1.811）、CTG（OR=0.432）和TGC（OR=1.771）与精神分裂症关联有统计学意义（P＜0.05）。 结论 CACNA1C基因多态性与精神分裂症及其临床表现有关联。

CACNA1C基因 精神分裂症 基因多态性

【Abstract】Objective To examine the relationship of calcium channel，voltage-dependent，L type，alpha 1C subunit （CACNAIC）gene polymorphism with schizophrenia.Method A total of 118 patients with schizophrenia and 122 healthy volunteers were selected in succession.Denaturing high performance liquid chromatography（DHPLC）was used to analyze the genotypes of CACNAIC gene（rs10848683，rs2238032 and rs2299661）.Medical record data of patients with schizophre⁃nia and the clinical manifestation of the patients（sensation and perception disorder，thought disorder，affective disorder and behavior disorder）were collected.The clinical phenotype databases of all patients were established.Result There were statistical differences for genotype and allele distribution of the rs2238032 and rs2299661 between patient group and control group（P＜0.05）.The TT genotype of rs2238032（OR=0.394）and the CG genotype of rs2299661（OR=0.326）associ⁃ated with the risk of schizophrenia.The genotype distribution of rs2238032 was related to the thought disorder，the emotion disorder and the PANSS score of schizophrenia patients（all P＜0.05）.The genotype distribution of rs2299661 was related to the perceptual disorders and PANSS score of schizophrenia patients（all P＜0.05）.Haplotype analysis showed that CTC （OR=1.811），CTG（OR=0.432）and TGC（OR=1.771）were significantly associated with schizophrenia（P＜0.05）.Conclu⁃sion The CACNA1C gene polymorphism is associated with schizophrenia and its clinical manifestations.

【Key words】CACNA1C Schizophrenia Polymorphism

遗传因素在精神分裂症发病中具有重要作用［1-2］。L型钙离子通道α1C亚基基因（calcium channel，L type，alpha1C subunit gene，CACNA1C）编码L型钙通道α1C亚基，该亚基可组装成CaV1.2钙离子通道蛋白［3］。研究表明，CACNA1C与神经系统树突形成、神经元存活、突触可塑性及记忆能力有关［4］。最近分子遗传学研究发现，CACNA1C的多态性及异常表达与精神分裂症显著相关，包括rs1006737、rs4765905、rs7297582等多个单核苷酸多态性（single nucleotide polymorphism，SNP）［5-8］。但是目前关于CACNA1C基因位点与精神分裂症关联的研究还存在分歧［10-11］。……